Hippocampal and entorhinal cortex neurofibrillary tangle formation in Guamanian Chamorros free of overt neurologic dysfunction.
Since first described, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam has represented an important model of age-related neurodegenerative disease. ALS/PDC is characterized neuropathologically by severe widespread involvement by neurofibrillary tangles (NFTs). Over the past 30 years there has been a dramatic decrease in the incidence of ALS and a 10-year increase in the age of onset of ALS and PDC. In 1979, Anderson et al reported evidence of significant NFT involvement in Guam natives who had been free of evidence of neurologic dysfunction. Using the slides from this study, we re-examined the extent of hippocampus and entorhinal NFT involvement and compared it to brains recently obtained from neurologically intact Guam natives and age-matched controls from New York. The tendency towards hippocampal and entorhinal NFT formation continues to be encountered among the inhabitants of Guam, particularly among those over age 50. although severe involvement was less commonly noted in relatively young individuals (< 50 years). As noted by Anderson et al, the pattern of neuropathologic lesions seen in those with extensive NFT involvement suggests that such cases represent preclinical examples of ALS/PDC in individuals who have yet to accumulate a sufficient burden of pathology to attract clinical attention and diagnostic evaluation.
Perl
Daniel P
DP
Neuropathology Division, Department of Pathology, Mount Sinai School of Medicine, Box 1134, One Gustave L. Levy Place, New York, NY 10029, USA. daniel.perl@mssm.edu
Hof
Patrick R
PR
Purohit
Dushyant P
DP
Loerzel
Arthur J
AJ
Kakulas
Byron A
BA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006141:Guam; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D009519:New York City; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000503:physiopathology; D015995:Prevalence; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology