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Phenotype of chromosome 14–linked familial Alzheimer's disease in a large kindred
Author(s) -
Lampe Thomas H.,
Bird Thomas D.,
Nochlin David,
Nemens Ellen,
Risse Steven C.,
Sumi S. Mark,
Koerker Richard,
Leaird Brie,
Wier Monna,
Raskind Murray A.
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410360308
Subject(s) - phenotype , senile plaques , dementia , genetics , myoclonus , cerebral amyloid angiopathy , alzheimer's disease , primary progressive aphasia , progressive myoclonus epilepsy , disease , pathology , biology , medicine , neuroscience , gene , frontotemporal dementia
We report the clinical and neuropathological features of chromosome 14–linked familial Alzheimer's disease (14qF AD) in affected members of the L family. Some clinical information on all 16 known affected individuals and detailed neuropathological findings in 6 family members were available for review. Common features of the phenotype of 14qFAD in the L family included onset of dementia before the age of 50, early progressive aphasia, early‐appearing myoclonus and generalized seizures, paratonia, cortical atrophy, numerous and extensive senile plaques and neurofibrillary tangles, and prominent amyloid angiopathy. Descriptions of phenotypic features were available for six additional recently defined 14q‐linked FAD kindreds: the findings in four of them (FAD4, FAD2, A, B) indicated a relatively consistently shared 14qFAD phenotype, conforming closely with the specific clinical and neuropathological characteristics noted in the L family. Comparisons also suggested several ostensible phenotypic variants in 14qFAD: (1) In two 14q‐linked kindreds (SNW/FAD3, FAD1), affected individuals in some instances were noted to survive to age 70 or beyond and the mean age at onset (> 49 years) in these two kindreds was somewhat higher than in their five 14qFAD counterparts (< 48 years in each) (2) in the SNW/FAD3 kindred, seizures and myoclonus were absent in all 10 subjects examined; and (3) cerebellar amyloid plaques were variably present within and among several 14qFAD kindreds. Comparisons with phenotypic features recently detailed in three kindreds (TOR3, F19, ROM) with codon 717 amyloid precursor protein gene mutations (i.e., APP 717 FAD) suggested several distinctions: Prominent progressive aphasia, myoclonus, seizures, and paratonia were all apparently less prevalent in APP 717 FAD, with language function predominantly spared over the initial disease course. The extent of homogeneity and heterogeneity in the clinical and neuropathological phenotype of 14q‐linked FAD and its possible meaningful distinctions from the phenotypes of APP 717 FAD await further determination.