Obsessive-compulsive disorder among schizophrenic patients: an exploratory study using functional magnetic resonance imaging data

The case of a 70-year-old woman with cerebral amyloid angiopathy (CAA) is presented. MRI of the head showed widespread miliary foci of haemorrhage within the cerebrum and cerebellum, with some additional linear lesions within the cerebral cortex and patchy lesions in the white matter. This is in contrast to the more usual pattern of intracranial haemorrhage in CAA, i.e., a lobar haematoma.     

Loss of vessel wall viability in cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Alzeheimer's disease and an important cause of cerebral haemorrhage in the elderly. CAA is characterized by the deposition of Alzheimer amyloid beta protein (A beta) in cerebral and leptomeningeal vessel walls. In order to study the effect of cerebrovascular A beta deposits in vivo, living canine leptomeninges obtained from old dogs affected by CAA were analysed by confocal laser scanning microscopy after immunofluorescence staining for A beta and viability staining with fluorescein diacetate (FDA). Simultaneous detection of the two signals showed a segmental loss of leptomeningeal vessel wall viability at some site of A beta deposition. Many of the non-viable vessels segments were also dilated, suggesting that A beta-induced vascular cell death creates the loci minores resistentiae for the development of cerebral haemorrhage in CAA.     

Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease

Cerebral amyloid angiopathy in Alzheimer's disease is characterized by deposition of amyloid beta (Abeta) in cortical and leptomeningeal vessel walls. Although it has been suggested that Abeta is derived from vascular smooth muscle, deposition of Abeta is not seen in larger cerebral vessel walls nor in extracranial vessels. In the present study, we examine evidence for the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain in Alzheimer's disease and that this contributes significantly to cerebral amyloid angiopathy. There is firm evidence in animals for drainage of interstitial fluid from the brain to cervical lymph nodes along periarterial spaces; similar periarterial channels exist in humans. Biochemical study of 6 brains without Alzheimer's disease revealed a pool of soluble Abeta in the cortex. Histology and immunocytochemistry of 17 brains with Alzheimer's disease showed that Abeta accumulates five times more frequently around arteries than around veins, with selective involvement of smaller arteries. Initial deposits of Abeta occur at the periphery of arteries at the site of the putative interstitial fluid drainage pathways. These observations support the hypothesis that Abeta is deposited in periarterial interstitial fluid drainage pathways of the brain and contributes significantly to cerebral amyloid angiopathy in Alzheimer's disease.     

Amyloid angiopathy as a clinico-pathological entity to consider in the differential diagnosis of any hemorrhagic cerebrovascular accident

Intracerebral hemorrhages represent about 10% of the whole of vascular cerebral accidents. According to different authors, the incidence of cerebral amyloid angiopathy varies between 5-10% and up to 20-30% of all primary non-traumatic intracerebral hemorrhages. This incidence was analyzed in our environment. A retrospective study was carried out on 403 patients, 203 of them were analyzed between 1990-91 and the other 200 between 1992-3. Age, arterial tension, relapses and localization were taken as criteria for a diagnosis. For the statistical analysis, Student's T-test was used for quantitative variables, while square Chi with Yates' correction was used for qualitative variables. Ischemic cerebral accidents (90.5% of the total) are more frequent than hemorrhagic cerebral accidents, which represent 5.7%. 3.7% were not registered. Therefore, it was suspected cerebral amyloid angiopathy in 1.4% of all vascular cerebral accidents. This represents 26.1% of the total of hemorrhagic patients. Different variables from groups of hemorrhagic vascular cerebral accidents were compared to those caused by amyloid cerebral angiopathy and significant statistics were found with respect to localization in the cerebral hemispheres (p < 0.01). Neither age, nor arterial tension or relapses were significant. Amyloid cerebral angiopathy as a cause of hemorrhagic cerebrovascular accident is and entity to be considered in the diagnosis of these patients. By using clinical criteria and others of localization through complementary explorations, a diagnosis for guessing such a process can be determined.     

Animal models of cerebral beta-amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a significant risk factor for hemorrhagic stroke in the elderly, and occurs as a sporadic disorder, as a frequent component of Alzheimer's disease, and in several rare, hereditary conditions. The most common type of amyloid found in the vasculature of the brain is beta-amyloid (A beta), the same peptide that occurs in senile plaques. A paucity of animal models has hindered the experimental analysis of CAA. Several transgenic mouse models of cerebral beta-amyloidosis have now been reported, but only one appears to develop significant cerebrovascular amyloid. However, well-characterized models of naturally occurring CAA, particularly aged dogs and non-human primates, have contributed unique insights into the biology of vascular amyloid in recent years. Some non-human primate species have a predilection for developing CAA; the squirrel monkey (Saimiri sciureus), for example, is particularly likely to manifest beta-amyloid deposition in the cerebral blood vessels with age, whereas the rhesus monkey (Macaca mulatta) develops more abundant parenchymal amyloid. These animals have been used to test in vivo beta-amyloid labeling strategies with monoclonal antibodies and radiolabeled A beta. Species-differences in the predominant site of A beta deposition also can be exploited to evaluate factors that direct amyloid selectively to a particular tissue compartment of the brain. For example, the cysteine protease inhibitor, cystatin C, in squirrel monkeys has an amino acid substitution that is similar to the mutant substitution found in some humans with a hereditary form of cystatin C amyloid angiopathy, possibly explaining the predisposition of squirrel monkeys to CAA. The existing animal models have shown considerable utility in deciphering the pathobiology of CAA, and in testing strategies that could be used to diagnose and treat this disorder in humans.     

Indications for surgery to determine the etiology of subcortical hemorrhage

We studied the etiology of subcortical hemorrhage in 55 patients (30 males, 25 females), aged 19-83 years (mean 60 years). CT scan was made in all patients on admission, with the use of intravenous infusion of contrast agent in 35 patients. Cerebral angiography was performed in 37 patients and MRI was performed in 22 patients. Forty-one patients underwent surgery and the other fourteen patients were treated conservatively. The cause of bleeding had been discovered before surgery in 12 cases; 10 arteriovenous malformations and 2 brain tumors. They were discovered by meticulous neuroradiological investigations including cerebral angiography, MRI, dynamic MRI, MRA and enhancing CT. The cause of bleeding was newly discovered after surgery in 7 cases; all of amyloid angiopathy. It remained unknown in the other 22 surgical cases although hypertensive angiopathy was suspected in eleven of them. Among the 14 patients who received conservative therapy, hemorrhagic diathesis including the use of Warfarin and DIC was the cause of bleeding in four cases and the etiology remained unknown in other ten, although hypertensive angiopathy was suspected in eight of them. The 32 patients in whom the etiology remained unknown had been observed as long as 12-120 months (mean, 40 months) and although bleeding has occurred at different locations in two of these patients, there has been no recurrence of bleeding at the same location in any of them. In conclusion, surgery is not indicated to determine the etiology of subcortical hemorrhage when meticulous neuroradiological investigations fail to disclose any vascular or tumorous lesions.     

Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).     

Obesity and diseases. 4. Molecular mechanism involved in the onset of arteriosclerosis in obesity]

BACKGROUND AND PURPOSE: The frequency of recurrent primary cerebral hemorrhage (RPCH), mainly in cases related to hypertension, has been considered low. This study investigated the frequency, mechanisms, and prognosis of RPCH. METHODS: We evaluated 359 patients with neuroimaging evidence of cerebral hemorrhage and selected 22 with RPCH. RESULTS: Five patients (23%) were older than 70 years at the first cerebral hemorrhage. Mean ages at the first and second hemorrhages were 60 and 63 years, respectively. Risk factors included hypertension (86%), diabetes (27%), and tobacco and alcohol use (each 14%). Hypocholesterolemia was demonstrated in 35% of the patients. The most common pattern of recurrent bleeding was ganglionic-ganglionic, mainly related to hypertension. Overall mortality was 32%. Forty-one percent and 27% of patients, respectively, had incapacitating and nonincapacitating sequelae; 2 of the latter had RPCH with a lobar location. Ganglionic-ganglionic hemorrhage was associated with a poor prognosis; otherwise, this pattern was uncommon in patients with nonincapacitating sequelae. Analysis of the control of risk factors, primarily hypertension after the first cerebral hemorrhage, disclosed that 56% of patients did not gain subsequent control. CONCLUSIONS: Rebleeding after a first primary intracerebral hemorrhage is not uncommon. The main topographic pattern of bleeding, ganglionic-ganglionic, is likely the result of hypertension; the less common lobar-lobar pattern probably results from amyloid angiopathy.     

Cerebral amyloid angiopathy. A review

Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in cerebral blood vessels. It occurs most frequently in association with clinical Alzheimer's disease but also occurs in some nondemented elderly people. CAA is a cause of spontaneous cerebral hemorrhage and may therefore present as a sudden unexpected death in an elderly person. The amyloid is deposited in cortical blood vessels, and on hematoxylin-eosin sections takes the form of pink hyaline thickening of arteries and arterioles, often with narrowing of the lumina. For diagnosis apple-green birefringence after Congo red staining is the most widely practiced and reliable tool. CAA-related hemorrhage may also occur in any lobe of the cerebrum close to the external surface and may occur at multiple sites and at the same or different times. CAA-related hemorrhage may occur in the setting of trauma necessitating distinction between the two and raising the question of whether it precipitated trauma or vice versa. Usually CAA-related hemorrhage is infrequent in sites where traumatic hemorrhages occur, and traumatic hemorrhages are often associated with other hemorrhages in sites typical for trauma. Five cases demonstrating many of the clinical and pathological features of CAA-related hemorrhage are presented. In two of the five cases, the hemorrhage followed trauma, suggesting that trauma as a precipitating factor for CAA-related hemorrhage may be more common than is generally recognized. CAA-associated hemorrhage should be considered in the differential diagnosis of cerebral hemorrhage in the elderly whether or not dementia is present.     

Use of fluorocitrate and fluoroacetate in the study of brain metabolism

Between 1984 and 1994, of the 375 patients admitted to our department for intracerebral hemorrhage (ICH), 24 (6.4%) had a recurrent ICH. There were 15 women and nine men and the mean age of the patients was 64.7 +/- 9.4 years (range 49-81) at the first bleeding episode and 68.7 +/- 7.5 years (range 57-83) at the second. The mean interval between the two bleeding episodes was 47.5 +/- 30.5 months (range 3 months to 14.8 years). Nine patients presented with more than one recurrence of ICH. Seventy-one percent of the patients were hypertensive. The site of the first hemorrhage was lobar in 17 patients, ganglionic (putamen, thalamus, or caudate nucleus) in six patients, and subdural in one. The recurrent hemorrhage occurred at a different location from the previous ICH. The most common pattern of recurrence was "lobar-lobar" (14 patients) and more rarely "ganglionic-ganglionic" (five patients), which was always observed in hypertensive patients. The outcome after the recurrent hemorrhage was usually poor, with severe cognitive impairment. By comparison with 81 patients followed up to 24 months (47.9 +/- 22.2 months) with isolated ICH without recurrence, only lobar hematoma and a younger age were risk factors for recurrences whereas sex and previous hypertension were not. The mechanisms of recurrence of ICH were multiple (hypertension, cerebral amyloid angiopathy). Control of blood pressure after the first hemorrhage may prevent ICH recurrences.     

A 67-year-old woman with polymyalgia rheumatica and left hemispatial neglect

We report 8 patients with the acquired immunodeficiency syndrome (AIDS) and intracerebral haemorrhage. There were 7 men and 1 woman (mean age 37.2 years) with a mean CD4 count of 81.2/mm3. Alcohol abuse was recorded in 7 patients, intravenous drug use in 4, homosexual activity in 2, thrombocytopaenia in 1 and severe hypertension in 1. There were 5 lobar and 3 deep haemorrhages. Potential aetiologies of intracerebral haemorrhage included cerebral toxoplasmosis (n = 2), thrombocytopenia (n = 2), hypertension (n = 1) and cerebral tuberculosis (n = 1). Data of these patients were compared with those of 30 AIDS inpatients without brain haemorrhage matched by age and sex and no statistically significant differences in risk factors for AIDS except for alcohol abuse (> 80 g/day) (p = 0.045) were found. Causes of brain haemorrhage in AIDS patients are heterogeneous. The relationship between both conditions may be explained by the effect of several predisposing factors to stroke in association with AIDS-related complications. Intracerebral haemorrhage is a late and serious complication of AIDS (mortality 62.5%). The frequency of intracerebral haemorrhage in AIDS (1.0%) is higher than that expected in a general population of young adults.     

Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management

BACKGROUND: Postpartum cerebral angiopathy as a cause of hemorrhagic stroke in young women is not well recognized. It is unknown whether this disorder represents a true inflammatory vasculitis or transient vasoconstriction related to the hormonal events of pregnancy and the postpartum period. CASE DESCRIPTION: A 39-year-old woman presented with postpartum intracranial hemorrhage and, 32 months later, with subarachnoid hemorrhage, following normal pregnancies. Cerebral angiography obtained after each stroke demonstrated diffuse irregularity of branches of the middle cerebral arteries consistent with a diffuse vasospastic process or classic vasculitis. Neurological deficits resolved and results of a transcranial Doppler study normalized after a short course of high-dose corticosteroids following the second stroke. CONCLUSIONS: Postpartum cerebral angiopathy should be considered in the differential diagnosis of recurrent intracranial hemorrhagic stroke in young women. Recognition of this condition may preclude treatment with potentially toxic therapies for vasculitis and will have important implications for counseling women on subsequent pregnancies.     

Glycogenolysis stimulation by non-steroidal anti-inflammatories in the perfused rat liver is not accompanied by Ca2+ release

To better understand the characteristics of amyloid deposition in the choroid plexus, we examined autopsied brain by routine histology, immunohistochemistry, and electron microscopy in three group of patients: primary systemic amyloidosis (n = 7), cerebral amyloid angiopathy (CAA, n = 6), and controls (n = 3). Three of the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid deposits of the choroid plexus were seen in six of the seven cases of systemic light chain amyloidosis. Immunohistochemistry revealed that the deposited amyloids had reactivity for immunoglobulin light chain and amyloid P component. Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils along the epithelial basement membrane as well as in the vascular walls was ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits were consistently present in meningeal blood vessels and were often found in senile plaques of the cerebral parenchyma; congophilic amyloid deposits were absent in the choroid plexus. Choroid plexus epithelial cells exhibited immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C-terminal-specific antibodies; in particular, consistent staining was obtained for the latter antibody. Immunoreactivity for amyloid beta protein (A beta) with monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial cells. These findings suggest that amyloid deposition of the choroid plexus depends on the major component protein in amyloidosis, and that the choroid plexus may produce APP and A beta protein although A beta amyloidosis is not evident in the choroid plexus.     

Respiratory-chain and pyruvate metabolism defects: Italian collaborative survey on 72 patients

Cerebral amyloid angiopathy (CAA) is a neuropathological feature of Alzheimer's disease and a common cause of cerebral hemorrhage in the elderly. The pathogenetic mechanisms leading to the deposition of Alzheimer amyloid beta-protein (A beta) in cortical and leptomeningeal vessel walls are unknown. There are no experimental models which reproduce the pathological changes of CAA. In this study, leptomeninges from young and old dogs with pre-existing CAA were cultured in cell culture medium or cerebrospinal fluid and their viability, histological appearance and metabolic activity were analyzed during the culture. In addition, living leptomeninges of old and young dogs were incubated with fluorescein-conjugated A beta and the uptake of A beta was studied by fluorescence microscopy. Leptomeninges from young and old dogs were viable up to 8 weeks in culture. They contain many small- and medium-sized arterioles, the main vessel type affected by CAA. Histology and immunohistochemistry showed excellent preservation of the vessel wall microarchitecture up to 4 weeks in culture. The cultures were metabolically active as shown by the de novo production of beta-amyloid precursor protein. Exogenously added A beta was focally deposited in the vessel walls of old, but not young dogs. In conclusion, the organ culture of canine leptomeninges is easy to perform and appears suitable to investigate the pathogenesis and the progression of CAA.     

Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type

BACKGROUND AND PURPOSE: Microvascular changes such as microaneurysms and fibrinoid necrosis have been found in the presence of cerebral amyloid angiopathy (CAA). These CAA-associated microvasculopathies (CAA-AM) may contribute to the development of CAA-associated hemorrhages and/or infarcts, hereafter referred to as "cerebrovascular lesions." Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is an autosomal dominant form of CAA, in which the amyloid angiopathy is pathologically and biochemically similar to sporadic CAA associated with aging and Alzheimer disease. To determine the significance of CAA-AM for CAA-associated cerebrovascular complications, we investigated the association between CAA-AM and cerebrovascular lesions in HCHWA-D patients. METHODS: In a previous autopsy study we semiquantitatively scored CAA-AM in 29 HCHWA-D patients. In the present study we reviewed clinical charts and autopsy protocols of these same patients. We investigated whether CAA-AM was associated with age at death, number of cerebrovascular lesions, duration of clinical illness, hypertension, and atherosclerosis. RESULTS: An association was found between CAA-AM and the number of cerebrovascular lesions (P = 0.009). The presence of microaneurysmal degeneration was most strongly associated with the number of cerebrovascular lesions (P < 0.001). In addition, we found an association between atherosclerosis and the CAA-AM score (P = 0.047). Hypertension was not associated with CAA-AM. CONCLUSIONS: Our findings support previous reports suggesting an important role of secondary microvascular degenerative changes in CAA-associated cerebrovascular lesions and suggest an aggravating effect of systemic atherosclerosis, but not hypertension, on the evolution of CAA-AM. These findings may be of relevance to understanding cerebrovascular complications of sporadic or Alzheimer disease-associated CAA.     

Delayed full-thickness grafting of lower leg defects following removal of skin malignancies

Cerebral stroke is a serious complication related to carotid endarterectomy (CEA), being most frequently caused by thromboembolic events and less frequently on account of cerebral haemorrhage. The present series comprised five out of 857 (0.6%) patients who had undergone CEA at Oulu University Hospital between the years 1974 and 1993 and suffered a postoperative stroke four to 13 days after surgery due to intracerebral haemorrhage (IH). Preoperatively, all these patients were neurologically intact, with transient ischaemic attacked (TIA) as the main indication for CEA. All five patients had a history of arterial hypertension treated adequately preoperatively, and one patient had high blood pressure levels after surgery. Critical ipsilateral stenosis of the internal carotid artery (> 90%) was detected in the preoperative angiogram in all five cases. The primary outcome after CEA was uneventful in every case, without any signs of neurological deficiency. The symptoms, comprising severe headache, convulsions and/or hemiparesis occurred suddenly four to 13 days (mean seven days) after CEA. The diagnosis of IH was based on computed tomography (CT) findings. All five patients were treated conservatively. Three of them died. We conclude that even normotensive, neurologically intact patients without demonstrable cerebral infarction or postoperative hypertension may suffer cerebral haemorrhage after the relief of high-grade carotid stenosis. The role of possible insufficiency of the autoregulatory mechanisms of the cerebral vasculature on account of long-standing critical stenosis of the internal carotid artery and subsequent uncontrolled hyperperfusion following CEA are discussed.     

Cooperative relaxation of supercoils and periodic transcriptional initiation within polymerase batteries

OBJECTIVE: To examine quantitatively white-matter changes at different sites in patients with definite vascular dementia and Alzheimer's disease. DESIGN: Prospective clinical and neuropathological series. SETTING: University Hospital clinics (Helsinki, Finland and London, Ontario). SUBJECTS: Twenty-two patients with a clinical and neuropathological diagnosis of vascular dementia and 20 patients with Alzheimer's disease. MEASURES: The frequencies of focal white-matter lesions, arteriolosclerosis, and cerebral amyloid angiopathy were assessed. Validated ratings and cell counts were done in the subcortical U-fiber, centrum semiovale, and periventricular areas of the frontal white matter. Degrees of abnormality (none, mild, moderate, severe) were rated for spongiosis (vacuolization of white matter), état criblé (widening of perivascular spaces), myelin loss, oligodendrocyte density, axonal loss, and overall. Densities of oligodendrocytes and astrocytes (cells per square millimeter) were determined. RESULTS: Patients with vascular dementia showed focal white-matter lesions and arteriolosclerosis more often than patients with Alzheimer's disease. The patients with vascular dementia also had significantly greater spongiosis (P<.001), état criblé (P=.004), myelin loss (P<.005) and overall white-matter abnormality (P<.001). Arteriolosclerosis was found in association with spongiosis but not with état criblé. Cerebral amyloid angiopathy did not appear to be related to any of the white-matter changes in patients with either vascular dementia or Alzheimer's disease. The U-fiber area showed fewer changes, and the periventricular area tended to be most affected. CONCLUSION: In addition to focal infarcts, patients with vascular dementia showed widespread diffuse changes, including spongiosis and arteriolosclerosis, along with état criblé and myelin loss. White-matter changes in patients with Alzheimer's disease could not be related to infarction. Pathologic changes in small blood vessels are associated with diffuse white-matter changes and may have a distinct role in the genesis of vascular dementia.     

An autopsy case of coexisting portal systemic encephalopathy and senile dementia of the Alzheimer type

An autopsy case of portal systemic encephalopathy and senile dementia of the Alzheimer type coexisting in a 77-year-old man is described. The patient had suffered recurrent episodes of delirium after a subtotal gastrectomy for gastric carcinoma. He died of DIC 45 months after the gastrectomy. A pathological examination revealed a vascular plexus around the liver which might have served as collateral circulation. Neuropathologically, spongy necrosis and Alzheimer type II changes of astrocytes were found in the basal ganglia and fronto-occipital cortices. In the same anatomical regions, only immunohistological staining using antibody against amyloid beta-protein and the periodic-acid methenamine silver method revealed abundant neuriticplaques, cerebral amyloid angiopathy and diffuse plaques. We discussed the clinicopathological findings in this case.     

Prion protein amyloidosis

The prion protein (PrP) plays an essential role in the pathogenesis of a group of sporadic, genetically determined and infectious fatal degenerative diseases, referred to as "prion diseases", affecting the central nervous system of humans and other mammals. The cellular PrP is encoded by a single copy gene, highly conserved across mammalian species. In prion diseases, PrP undergoes conformational changes involving a shift from alpha-helix to beta-sheet structure. This conversion is important for PrP amyloidogenesis, which occurs to the highest degree in the genetically determined Gerstmann-Str?ussler-Scheinker disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA), while it is less frequently seen in other prion diseases. GSS and PrP-CAA are associated with point mutations of the prion protein gene (PRNP); these conditions show a broad spectrum of clinical presentation, the main signs being ataxia, spastic paraparesis, extrapyramidal signs and dementia. In GSS, parenchymal amyloid may be associated with spongiform changes or neurofibrillary lesions; in PrP-CAA, vascular amyloid is associated with neurofibrillary lesions. A major component of the amyloid fibrils in the two diseases is a 7 kDa peptide, spanning residues 81-150 of PrP.