INTRAFAMILIAL DIVERSITY OF PHENOTYPE ASSOCIATED WITH APP DUPLICATION

Abstract

Different APP locus duplications have been recently identified in rare families with autosomal dominant early onset Alzheimer disease (AD) and Aβ-related cerebral amyloid angiopathy (CAA).1–3 We report a novel family revealing a very large diversity of phenotype including dementia with Lewy bodies (DLB). ### Methods. Family members gave informed consent according to a protocol approved by the ethics committees of the CCPPRB Pitie-Salpetriere and Paris-Necker. Characterization of five patients, with two detailed neuropsychological evaluations, brain MRI of three patients, and one neuropathologic evaluation, were assessed. APP locus was analyzed by quantitative multiplex PCR of short fluorescent fragments (QMPSF) in three patients. Patients were considered affected if they had dementia, intracerebral hemorrhage (ICH), or epilepsy (e-Methods on the Neurology ® Web site at www.neurology.org). ### Results. The proband (II-1, figure e-1) developed bradykinesia, memory problems, and apraxia when she was 44 years old. She developed paranoid delusion with visual hallucinations at 50 years of age. The association with bilateral tremor, rigidity, and bradykinesia was suggestive of DLB. Several T2 lesions were noted on MRI. She died at 55 years of age. Patients I-2 and I-3 had progressive memory disturbances with behavioral changes suggestive of AD since they were 55 and 60 years of age. Patient II-3 had partial visual seizures at the age …