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J Alzheimers Dis. 2015;47(3):715-28. doi: 10.3233/JAD-150307.

Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition.

Author information

1
Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
2
Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
3
Division of Geriatrics, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA.
4
Veterans Affairs Medical Center-St. Louis, St. Louis, MO, USA.

Abstract

Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain.

KEYWORDS:

Alzheimer’s disease; cognition; insulin; intranasal administration

PMID:
26401706
PMCID:
PMC6080853
DOI:
10.3233/JAD-150307
[Indexed for MEDLINE]
Free PMC Article

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