Year: 2012
Type: article
Study design: Case Report
Abstract: Lowenberg and Waggoner in 1934 reported 5 members from 2 generations of a Michigan family with onset of dementia early in the 4th decade of life. Although the published pathology appeared to indicate AD, affected members had several unusual features, including unsteady gait, seizures, spasticity, and extensive neuritic plaques in the basal ganglia, raising uncertainty about the appropriate classification of this family. Two affected individuals studied clinically at the University of Michigan during the 1990s were identified as being descendents of that family. Both individuals were found to have a PSEN1 gene mutation (I143T). Two affected siblings of this kindred were studied clinically, neuroradiologically, and neuropathologically using established protocols and procedures typically used in NIA-funded Alzheimer's disease centers. PET imaging studies were carried out using 18 F-2-fluoro-2-deoxy-D-glucose (18 F-FDG). Affected individuals presented personality changes and memory loss beginning in the middle of the fourth decade of life. Seizures were also common. The disease duration ranged from 2 to 7 years. We identified metabolic abnormalities with PET scanning including typical pattern of temporoparietal hypometabolism and cerebellar hypometabolism. Neuropathologic studies of both siblings revealed numerous Aβ-immunopositive neuritic and cotton wool plaques in the cerebral cortex. Abundant Aβ deposits were also present in subcortical nuclei and cerebellum. Amyloid deposits were seen in the subcortical white matter. Amyloid angiopathy was severe in the cerebral and cerebellar cortices. Immunohistochemical studies using a panel of antibodies raised against several amyloid β epitopes suggest that there is deposition of truncated amino-terminal Aβ fragments. Tau-immunostaining revealed neurofibrillary tangles and neuropil threads in the neocortex, hippocampus and some subcortical nuclei. The clinical and neuropathologic phenotypes of familial Alzheimer's disease association with mutation PSEN1 I143T are described. The original description by Lowenberg and Waggoner and the current results are of interest in defining the natural history of the disease. In two families, one reported in Belgium and one in Sweden, the clinical phenotype appears similar to that seen in the individuals reported here.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2043778784