Cited by 420Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Reversible memory loss in a mouse transgenic model of Alzheimer’s disease

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Kotilinek, Linda A., Bacskai, Brian, Westerman, Marcus, Kawarabayashi, Takeshi, Younkin, Linda, Hyman, Bradley T., Younkin, Steven, Ashe, Karen H.·2002·The Journal of Neuroscience

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition, believed to be irreversible, characterized by inexorable deterioration of memory and intellect, with neuronal loss accompanying amyloid plaques and neurofibrillary tangles. In an amyloid precursor protein transgenic mouse model, Tg2576, little or no neuronal loss accompanies age-related memory impairment or the accumulation of Abeta, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain Abeta and memory in Tg2576 mice stratified by age (Westerman et al., 2002). Broadening the age range examined obscured this relationship, leading us to propose that small, soluble assemblies of Abeta disrupt cognitive function in these mice. Here we show that memory loss can be fully reversed in Tg2576 mice using intraperitoneally administered BAM-10, a monoclonal antibody recognizing the N terminus of Abeta. The beneficial effect of BAM-10 was not associated with a significant Abeta reduction, but instead eliminated the inverse relationship between brain Abeta and memory. We postulate that BAM-10 acts by neutralizing Abeta assemblies in the brain that impair cognitive function. Our results indicate that a substantial portion of memory loss in Tg2576 mice is not permanent. If these Abeta assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients.

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Crossref · 10.1523/jneurosci.22-15-06331.2002

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  • The oligomer hypothesis predicted that early memory loss should be reversible, and this prediction was confirmed in transgenic mouse experiments.

    “Based on a central role for impaired signaling, the oligomer hypothesis predicted that early memory loss should be reversible. This prediction was confirmed in the transgenic mouse experiments mentioned above (Dodart et al., 2002; Kotilinek et al., 2002).”

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Authors
Kotilinek, L. A., Bacskai, B., Westerman, M., Kawarabayashi, T., Younkin, L., Hyman, B. T., Younkin, S., & Ashe, K. H.
Affiliations
  • University of Minnesota (US)
  • Harvard University (US)
  • Mayo Clinic (US)
  • Mayo Clinic in Florida (US)
Venue
The Journal of Neuroscience
Published
2002-08-01
Volume
22
Issue
15
Pages
6331-6335
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1705725530
Cited by
420
References
13
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 6 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 15 · 2013: 28 · 2012: 14
FWCI
18.41
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association
  • National Institutes of Health
  • National Institute on Aging (P01AG015453)
  • National Institute of Mental Health (R01MH065465)
  • National Institute of Neurological Disorders and Stroke (R01NS033249)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, memory loss, amyloid-beta, monoclonal antibodies, Tg2576 mice, amyloid precursor protein, cognitive function, age-related memory impairment
MeSH terms
Aging, Alzheimer Disease, Animals, Antibodies, Monoclonal, Behavior, Animal, Brain Chemistry, Cognition, Disease Models, Animal, Female, Immunization, Passive, Injections, Intraperitoneal, Male, Memory, Memory Disorders, Mice, Transgenic, Remission Induction, Spatial Behavior, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice

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