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May 1, 2012

Insulin and Alzheimer Disease—Reply

Author Affiliations

Author Affiliation: Veterans Affairs Puget Sound Healthcare System, University of Washington School of Medicine, Seattle, Washington.

Arch Neurol. 2012;69(5):670-671. doi:10.1001/archneurol.2012.45

In reply

In their interesting commentary, Dandona and colleagues highlight several of the potential mechanisms through which insulin may modulate Alzheimer disease (AD) pathologic processes. Indeed, one of the attractive features of insulin as a therapeutic agent for AD is that it affects multiple pathways of direct relevance to AD pathophysiology. Numerous points of interaction between insulin and amyloid processing have been identified including modulation of amyloid-related gene expression in peripheral mononuclear blood cells as observed by Dandona et al, regulation of proteases and lipoproteins related to amyloid clearance, and protection against amyloid toxicity.1,2 Insulin-related effects on inflammation, tau phosphorylation, and vascular function are other pathways that may influence the expression of AD pathology.3 These findings, combined with growing evidence of reduced insulin availability or action in the central nervous system of patients with AD, provide a rationale for therapeutic approaches that target insulin delivery to the brain.

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