Congophilic angiopathy of the brain: a clinical and pathological report on two siblings.

Abstract

SUMMARY Clinical and histological accounts are given of a sister and brother, dying aged 61 and 56 years respectively after illnesses lasting 5-6 years marked by a progressive mental and physical disability. The family history suggested transmission by a dominant gene. The histological findings were of a very severe congophilic angiopathy confined to the brain, spinal cord and leptomeninges and giving rise to multiple haemorrhages and softenings. There were, in addition, abundant amyloid-containing "plaques" of various forms, found principally in the hippocampus and cerebellar cortex. The cases are compared with similar cases in the literature, and reasons given for regarding this condition as a separate entity rather than a variant of Alzheimer's disease.In 1940' and 19442 Worster-Drought, Greenfield and McMenemey described a family of which 10 members, male and female, over three generations, suffered from a progressive paralysis, associated in most cases with dementia. The onset was usually in the fifth decade, and the mean duration of the illness was about 9 years. Two affected siblings came to necropsy, and showed very similar lesions in the brain, consisting of "hyaline" changes in small blood vessels and peculiar "plaques", up to 100 um in diameter, in the hippocampus and cerebellar cortex. They labelled the condition Familial presenile dementia with spastic paralysis, and regarded it as a new entity, clearly separable from previously described dementing processes. They considered, and rejected, the idea that it was somehow related to Alzheimer's disease. Such a relationship, however, was suspected by later authors, who observed that in cases resembling those described by WorsterDrought et al there was a florid cerebral amyloid angiopathy, not associated with amyloidosis in the rest of the body, recalling, though generally far exceeding, the amyloid angiopathy frequently observed in cases of Alzheimer's disease.We shall discuss the quesion of-classification later in this paper, having first given a clinical and pathological account of a sister and brother whose illness was clearly the same as that described by Worster-Drought et al.

Vascular Variant of Alzheimer's Disease Characterized by Severe Plaque-Like β Protein Angiopathy

“…This was in contrast with the other cases of severe CAA coexisting with AD where such lesions were found occasionally in a pari o f the vessels with CAA: Similar cases of dementia characterized by severe CAA with perivascular plaque formation have been reported [9,[24][25][26][27][28][29][30][31]. The reported cases were familial [24-26, 29, 30] or nonfamilial [9,27,28,31]; NFT were present [9,[24][25][26][29][30][31] or absent [27,28]. Some have been discussed as atypical AD [26,31], and others as the other entities including 'primary idiopathic cerebrovascular amyloidosis' [28].…”

“…The clinical and pathological heterogeneity in those patients [9,[24][25][26][27][28][29][30][31] may reflect the molecular difference of cerebrovascu lar amyloid proteins. In a British familial CAA character ized clinically by dementia, spastic paresis, and ataxia, and pathologically by CAA with nonneuritic plaque for mation [24,25,29,30], the amyloid protein was recently reported not to be [3 protein, but a novel protein [48], Recently, a Japanese demented patient presented with PrP amyloid angiopathy and NFT in association with codon 145 mutation of the PrP gene [9]. In our case, the deposited amyloid protein was inimunohistochemically demonstrated to be P protein; the case was considered to be a variant of AD characterized by the peculiar neuropa thological feature, severe plaque-like angiopathy.…”

Modeling familial British and Danish dementia

“…In 1933, Worster-Drought first described a British kindred with presenile dementia and spastic paralysis (WorsterDrought et al 1933(WorsterDrought et al , 1944, and subsequently an identical condition was reported in two siblings (Griffiths et al 1982). Both families were later shown to be part of the same pedigree.…”

Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia

“…Familial British dementia, an autosomal dominant neurodegenerative disorder, is characterized by progressive spastic tetraparesis, cerebellar ataxia and dementia 2,3 . The principal pathological hallmarks of FBD include the presence of non-neuritic plaques and amyloid angiopathy in the cerebellum, hippocampus, amygdala and cerebral cortex, hippocampal neurofibrillary tangles and ischemic white matter changes [1][2][3] .…”