Aged non-human primates: an animal model of age-associated neurodegenerative disease.
Aged non-human primates develop age-associated behavioral and brain abnormalities similar to those that occur in aged humans and, to a greater extent, in individuals with Alzheimer's disease. Declines in performance on cognitive and memory tasks begin at the monkey equivalent of late-middle life. As occurs in elderly humans, significant differences have been demonstrated in levels of performance between animals within older age groups. The brains of old monkeys show degenerative changes in neurons, abnormal axons and neurites (particularly in telencephalic areas), and deposits of amyloid in senile plaques and around blood vessels. Moreover, in some older animals, decrements occur in markers of specific neurotransmitter circuits, including the basal forebrain cholinergic system. It has been suggested that alterations in these cholinergic neurons contribute to the memory deficits that occur in older individuals. Because axotomy-induced retrograde degeneration of these neurons can be prevented by the administration of nerve growth factor, we have begun studies to determine whether administration of nerve growth factor improves performance of aged animals on memory tasks. This review describes the complementary nature of studies of non-human primates and human subjects, illustrating how these investigations can clarify factors that influence behavior and brain biology in age-associated diseases.
Price
D L
DL
Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205-2181.
Martin
L J
LJ
Sisodia
S S
SS
Wagster
M V
MV
Koo
E H
EH
Walker
L C
LC
Koliatsos
V E
VE
Cork
L C
LC
D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease; D017772:Amyloid Neuropathies / Q000473:pathology / Q000523:psychology / Q000662:veterinary; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001927:Brain Diseases / Q000473:pathology / Q000523:psychology / Q000662:veterinary*; D003704:Dementia; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000473:pathology*; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D011597:Psychomotor Performance; D012453:Saimiri
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents