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- W1998929086 abstract "The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the Aβ peptides, which accumulate as β-amyloid plaque in the brain during Alzheimer's disease (AD). Synaptic activity has been shown to increase APP processing and Aβ production, and it is generally believed that Aβ, particularly Aβ oligomers, have deleterious effects on synaptic function. We have examined the in vivo role of endogenous Aβ in learning and memory consolidation by manipulating Aβ levels in the hippocampus of rats using a newly generated anti-rodent Aβ monoclonal antibody, antibody m3.2. Antibody m3.2 recognizes non-denatured rodent Aβ within residues 10–15, binds both rodent Aβ1–40 and Aβ1–42, and does not bind to human Aβ. Bilateral hippocampal injections of 1 μg of antibody m3.2 in 1 μl isotonic saline before, but not after, training significantly disrupted inhibitory avoidance memory formation in rat. Injection of a control antibody had no effect. We co-injected human Aβ1–42 along with antibody m3.2 to determine whether exogenous Aβ rescues the amnesia caused by antibody m3.2. Co-injection of 200 pM human Aβ1–42, which we determined by ELISA to be similar to the concentration of Aβ1–42 in the hippocampus of the rat, restored inhibitory avoidance memory formation. Furthermore, hippocampal administration of exogenous human Aβ1–42 at this physiological concentration without antibody m3.2 enhanced memory retention above baseline. Our findings suggest that Aβ should not only be regarded as a synapto-toxic factor to be reduced in the CNS in order to avoid AD pathogenesis, but that it plays a critical role at physiological concentrations as a positive modulator of learning and/or an early phase of memory consolidation in the normal brain. Indeed, disruption or dysregulation of the normal function of Aβ during AD pathogenesis may be one of the underlying causes of synaptic dysfunction in the disease. (Supported by the NINDS, NS045205, and the Alzheimer's Association, IIRG-07–60047, to PMM; and by the NIMH, MH65635, to CMA." @default.
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- W1998929086 date "2008-07-01" @default.
- W1998929086 modified "2023-10-18" @default.
- W1998929086 title "O2-02-01: Endogenous Aβ enhances memory retention in the rat" @default.
- W1998929086 doi "https://doi.org/10.1016/j.jalz.2008.05.313" @default.
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