P2-431: NEUROPATHOLOGY OF EARLY-ONSET FAMILIAL ALZHEIMER'S DISEASE CAUSED BY PRESENILIN-1 MISSENSE MUTATION THR116ASN

The majority (∼55%) of early-onset familial Alzheimer's disease (FAD) is caused by mutations in the presenilin 1 gene (PSEN1). Here we describe a family with early onset FAD with a missense mutation in thePSEN1 gene (Thr116Asn). Five family members developed dementia in the third decade of life. One subject underwent autopsy. Clinical examination, genetic analysis and CSF sampling were performed during the life. Tissue sampling and immunohistochemistry on paraffin sections were performed post mortem. The onset of clinical symptoms occurred at the age of 37 years, and the disease progressed rapidly. The clinical picture was characterized by progressive memory impairment, amnestic aphasia, and gait disturbances. Neuropathological assessment revealed widespread β-amyloid (Thal phase 5) and tau (Braak stage 6) pathology. Abundant deposition of diffuse and cored plaques were distributed in cortical and subcortical areas, as well as in the cerebellum. Cotton wool plaques were observed mainly in the occipital cortex. Cerebral amyloid angiopathy was present throughout the brain. In the neocortex, tau pathology, especially neuropil threads were more abundant in the frontal and occipital cortex and in the hippocampus. No α-synuclein or TDP-43 pathology was found in cortical or subcortical areas. Here, we present the first comprehensive neuropathological study of early-onset FAD with a missense mutation Thr116Asn in the presenilin 1 gene. In contrast to other PS1-linked AD patients, the present subject developed cotton wool plaques which were not associated with spastic paraparesis.