Evidence that aging and amyloid promote microglial cell senescence.
Advanced age and presence of intracerebral amyloid deposits are known to be major risk factors for development of neurodegeneration in Alzheimer's disease (AD), and both have been associated with microglial activation. However, the specific role of activated microglia in AD pathogenesis remains unresolved. Here we report that microglial cells exhibit significant telomere shortening and reduction of telomerase activity with normal aging in rats, and that in humans there is a tendency toward telomere shortening with presence of dementia. Human brains containing high amyloid loads demonstrate a significantly higher degree of microglial dystrophy than nondemented, amyloid-free control subjects. Collectively, these findings show that microglial cell senescence associated with telomere shortening and normal aging is exacerbated by the presence of amyloid. They suggest that degeneration of microglia is a factor in the pathogenesis of AD.
Flanary
Barry E
BE
Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, Florida 32610-0244, USA.
Sammons
Nicole W
NW
Nguyen
Cuong
C
Walker
Douglas
D
Streit
Wolfgang J
WJ
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D000682:Amyloid / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D016615:Telomere
D000682:Amyloid