Lampe T H, Bird T D, Nochlin D, Nemens E, Risse S C, Sumi S M, Koerker R, Leaird B, Wier M, Raskind M A
Geriatric Research, Education, and Clinical Center, American Lake Department of Veterans Affairs Medical Center, Tacoma, WA 98493.
Ann Neurol. 1994 Sep;36(3):368-78. doi: 10.1002/ana.410360308.
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.
我们报告了L家族中受影响成员的14号染色体连锁型家族性阿尔茨海默病（14qFAD）的临床和神经病理学特征。我们可以查阅所有16名已知受影响个体的一些临床信息，以及6名家族成员详细的神经病理学发现。L家族中14qFAD表型的共同特征包括50岁前出现痴呆、早期进行性失语、早期出现的肌阵挛和全身性癫痫、僵人综合征、皮质萎缩、大量广泛的老年斑和神经原纤维缠结，以及显著的淀粉样血管病。另外还有6个最近定义的14q连锁型FAD家族的表型特征描述：其中4个家族（FAD4、FAD2、A、B）的发现表明存在相对一致的共享14qFAD表型，与L家族中 noted的特定临床和神经病理学特征密切相符。比较还表明14qFAD存在几种明显的表型变异：（1）在两个14q连锁家族（SNW/FAD3、FAD1）中，某些情况下受影响个体存活至70岁或以上，这两个家族的平均发病年龄（>49岁）略高于其他5个14qFAD家族（每个家族<48岁）；（2）在SNW/FAD3家族中，所检查的10名受试者均未出现癫痫和肌阵挛；（3）在几个14qFAD家族内部和之间，小脑淀粉样斑的出现情况各不相同。与最近在3个携带密码子717淀粉样前体蛋白基因突变的家族（TOR3、F19、ROM，即APP717 FAD）中详细描述的表型特征进行比较，发现了一些差异：在APP717 FAD中，明显进行性失语、肌阵挛、癫痫和僵人综合征都不太常见，在疾病初期语言功能基本未受影响。14q连锁型FAD临床和神经病理学表型的同质性和异质性程度，以及它与APP717 FAD表型可能存在的有意义差异，还有待进一步确定。
