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| PHENOTYPE OF CHROMOSOME 14-LINKED FAMILIAL ALZHEIMERS-DISEASE IN A LARGE KINDRED |
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| Author(s): LAMPE TH, BIRD TD, NOCHLIN D, NEMENS E, RISSE SC, SUMI SM, KOERKER R, LEAIRD B, WIER M, RASKIND MA |
| Source: ANNALS OF NEUROLOGY Volume: 36 Issue: 3 Pages: 368-378 Published: SEP 1994 |
| Times Cited: 88 References: 36 |
| Abstract: 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., 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: LAMPE, TH (reprint author), AMER LAKE DEPT VET AFFAIRS MED CTR, CTR GERIATR RES EDUC & CLIN, TACOMA, WA 98493 USA |
Addresses:
1. UNIV WASHINGTON, SCH MED, DEPT PSYCHIAT & BEHAV SCI, SEATTLE, WA 98195 USA
2. UNIV WASHINGTON, SCH MED, DEPT MED NEUROL, SEATTLE, WA USA
3. UNIV WASHINGTON, SCH MED, DEPT PATHOL NEUROPATHOL, SEATTLE, WA USA
4. DEPT VET AFFAIRS MED CTR, SEATTLE, WA 98108 USA |
| Publisher: LITTLE BROWN CO, 34 BEACON STREET, BOSTON, MA 02108-1493 |
| Subject Category: Clinical Neurology; Neurosciences |
| IDS Number: PF966 |
| ISSN: 0364-5134 |
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