APOLIPOPROTEIN-E IN GUAMANIAN AMYOTROPHIC-LATERAL-SCLEROSIS PARKINSONISM-DEMENTIA COMPLEX - GENOTYPE ANALYSIS AND RELATIONSHIPS TO NEUROPATHOLOGICAL CHANGES

Apolipoprotein E (Ape E) has been recently identified within amyloid d eposits and neurofibrillary tangles in the brains of Alzheimer's disea se (AD) patients. A strong association of the Apo E epsilon 4 allele w ith higher risk of developing AD has also been reported. In the presen t study, the distribution of Apo E and the possible relation ship betw een Apo E alleles and neuropathological alterations were analyzed in a series of Guamanian amyotrophic lateral sclerosis/parkinsonism-dement ia complex (ALS/PDC) cases, a neurodegenerative condition characterize d neuropathologically by widespread, severe neurofibrillary tangle for mation but rare amyloid deposits. ApoE immunoreactivity was consistent ly observed in both type of lesions in these cases. Compared to tau pr otein immunoreactivity, there were generally fewer Apo E-immunoreactiv e neurofibrillary tangles, particularly in the deep layers of the neoc ortex and in the hippocampus. Genotype analysis revealed that the epsi lon 4 allele frequency was 5.9%, the epsilon 3 allele frequency 88.2%, and the epsilon 2 allele frequency 5.9% in this series. Recent data s uggest that the Apo E4 variant may induce amyloidogenesis, while E2 co uld have a neuroprotective role. However, the rare Guamanian patients with amyloid deposits in cortical areas were not related to the epsilo n 4 allele, since all cases with senile plaques were epsilon 3/epsilon 3. In addition, compared to unaffected Guamanian cases and other Asia n-Pacific populations previously reported, the observed low frequency of the epsilon 2 allele in the present cases, which may be consistent with the notion that this allele, may represent a neuroprotective fact or in several neurodegenerative disorders. The present data indicate t hat there is a strong interaction between Apo E deposition and neurofi brillary changes in Guamanian ALS-PDC.