We report the clinical and neuropathological features of chromosome 14-linked familial
Alzheimer's disease (14qFAD) 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.,
APP717 FAD) suggested several distinctions: Prominent
progressive aphasia,
myoclonus,
seizures, and paratonia were all apparently less prevalent in
APP717 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
APP717 FAD await further determination.