Linking cognition to age and amyloid-β burden in the brain of a nonhuman primate (Microcebus murinus)

The gray mouse lemur (Microcebus murinus) is a valuable model in research on age-related proteopathies. This nonhuman primate, comparable to humans, naturally develops tau and amyloid-β proteopathies during aging. Whether these are linked to cognitive alterations is unknown. Here, standardized cogni...

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Veröffentlicht in:Neurobiology of aging 2020-10, Vol.94, p.207-216
Hauptverfasser: Schmidtke, Daniel, Zimmermann, Elke, Trouche, Stéphanie G., Fontès, Pascaline, Verdier, Jean-Michel, Mestre-Francés, Nadine
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Sprache:eng
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Zusammenfassung:The gray mouse lemur (Microcebus murinus) is a valuable model in research on age-related proteopathies. This nonhuman primate, comparable to humans, naturally develops tau and amyloid-β proteopathies during aging. Whether these are linked to cognitive alterations is unknown. Here, standardized cognitive testing in pairwise discrimination and reversal learning in a sample of 37 aged (>5 years) subjects was combined with tau and amyloid-β histochemistry in individuals that died naturally. Correlation analyses in successfully tested subjects (n = 22) revealed a significant relation between object discrimination learning and age, strongly influenced by outliers, suggesting pathological cases. Where neuroimmunohistochemistry was possible, as subjects deceased, the naturally developed cortical amyloid-β burden was significantly linked to pretraining success (intraneuronal accumulations) and discrimination learning (extracellular deposits), showing that cognitive (pairwise discrimination) performance in old age predicts the natural accumulation of amyloid-β at death. This is the first description of a direct relation between the cortical amyloid-β burden and cognition in a nonhuman primate. •Age predicts cognitive performance in old mouse lemur primates.•Low performers may represent pathological cases.•Extracellular cortical accumulations of amyloid-β are linked to impaired discrimination learning.•Subjects presenting with intraneuronal amyloid-β fail more often in a pretraining task.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2020.03.025