Lack of correlation between plaque burden and cognition in the aged monkey

Abstract

To assess whether amyloid plaque accumulation in the monkey brain can account for age-related cognitive impairment that begins at about 20 years of age, we measured plaque content in the brains of 14 rhesus monkeys aged 5-30 years. We used immunohistochemistry employing the monoclonal antibody 6E10, which is specific to amino acids 1-17 of the amyloid beta peptide to identify amyloid plaques in serial coronal sections of the forebrain. Amyloid plaques accumulate with age, starting at 25 years of age and escalating after 30 years. Until the age of 30, plaques are only found in a few monkeys and are relatively sparse. Results from our group and others show that plaque content and the proportion of individuals afflicted with amyloid plaques increase with age. Although both cognitive dysfunction and plaque content increase with age, amyloid plaque content does not correlate with the cognitive dysfunction observed in elderly monkeys since even in very old subjects some cognitively impaired animals have few amyloid plaques and others with abundant plaques show only minor cognitive impairments. In summary, amyloid plaques appear to accumulate significantly only in monkeys over 25 years of age but do not appear to be a causal factor in age-related cognitive decline of the normal aging rhesus monkey.

Long-Term Potentiation Is Impaired in Middle-Aged Rats: Regional Specificity and Reversal by Adenosine Receptor Antagonists

“…One recent study found progressively greater impairments across subjects from 30 to 90 years of age (Davis et al, 2003), whereas another reported a steady decrease across multiple measures of memory in healthy adults from age 20 forward (Park et al, 2003). Declines in memory from young adulthood to middle age have also been described previously for rats (Deupree et al, 1993;Granger et al, 1996;Oler and Markus, 1998;Ward et al, 1999;Meneses et al, 2004) and monkeys (Herndon et al, 1997;Sloane et al, 1997), suggesting that this effect could be a general feature of mammalian brain. These observations raise the question of whether long-term potentiation (LTP), a form of synaptic plasticity widely regarded as a substrate of memory encoding, also begins to deteriorate relatively early in adult life.…”

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

“…Although amyloid plaques are frequently observed, in contrast to Alzheimer's disease, the ratio of amyloid β peptide 40 and 42 in the aged monkeys favors the shorter, less pathogenic form (Gearing et al 1996). While the accumulation of amyloid β plaques increases after age 25 in rhesus monkeys, the plaque content does not correlate with cognitive dysfunction, as measured by a standardized score derived from DNMS, spatial/color DRST, and spatial/object RL (Sloane et al 1997). The number of amyloid β plaques also fails to correlate with DR performance (Cork 1993).…”

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…In addition, the amyloid plaques that do accumulate do not show the distribution typical of AD or evidence of a predilection for the hippocampus and entorhinal cortex (Heilbroner and Kemper 1990). Additionally, there is no relationship between the accumulation of amyloid plaques and cognitive impairments (Sloane et al 1997). Finally, neurofibrillary tangles are a second critical and diagnostic feature of AD that is particularly related to the death of neurons but there is no clear evidence that neurofibrillary tangles are ever present in the rhesus monkey brain (Kimura et al 2003;and Finch and Austad, this publication).…”