Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease
Open accessAbstract
We examined the relationships between normal aging, Alzheimer's disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60-79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60-79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD.
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At some level, the burden of pathology becomes great enough to overcome the protective mechanism of reserve, resulting in rapid cognitive decline.
“Possibly, at some level, the burden of pathology becomes great enough to overcome this protective mechanism, resulting in rapid cognitive decline31,53.”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [31]
The Discussion describes a possible protective role for sex hormones against Alzheimer’s pathology, but does not discuss cognitive reserve, a pathology threshold that overcomes it, or rapid cognitive decline. Searches for reserve and pathology-threshold language found no passage addressing that proposed sequence. (LLM, conf=0.77)
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- Authors
- Rosario, E. R., Chang, L., Head, E. H., Stanczyk, F. Z., & Pike, C. J.
- Affiliations
- University of Southern California (US)
- University of California, Irvine (US)
- Corresponding author
- Pike, Christian J.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 32
- Issue
- 4
- Pages
- 604-613
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2930132
- OpenAlex
- W2150576468
- Cited by
- 289
- References
- 82
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 11 · 2023: 19 · 2022: 15 · 2021: 25 · 2020: 21 · 2019: 27 · 2018: 22 · 2017: 23 · 2016: 20 · 2015: 17 · 2014: 16 · 2013: 14 · 2012: 13
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG05 128, AG05131, AG 05142, AG 16573, P50AG005131, P50AG005128, P50AG016573, AG23739, R01AG023739, P50AG005142)
- National Institute of Neurological Disorders and Stroke (F31NS052143, NS05214301)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- sex hormones, Alzheimer's disease, normal aging, androgens, estrogen, testosterone, postmenopausal women, sex differences, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Androgens, Brain, Enzyme-Linked Immunosorbent Assay, Estrogens, Female, Humans, Male, Middle Aged, Radioimmunoassay, Linear Models, Amyloid beta-Peptides
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