Selected Grantee Publications
- Clear All
- 3 results found
- Alzheimer's Disease
- S10 [SIG, BIG, HEI]
Effect of Hormone Replacement Therapy on Amyloid Beta (Aβ) Plaque Density in the Rhesus Macaque Amygdala
Appleman et al., Frontiers in Aging Neuroscience. 2024.
https://www.frontiersin.org/articles/10.3389/fnagi.2023.1326747/full
Amyloid beta plaque density is associated with Alzheimer’s disease. In this study, the authors examined its concentration in aged female nonhuman primates’ cerebrospinal fluid, as well as in the amygdala, an area of the brain involved with emotion and memory. They set out to test the hypothesis that estrogen hormone replacement therapy can beneficially affect amygdala Aβ plaque density in “surgically menopausal” females (i.e., aged rhesus macaques that had undergone ovariectomy). Female rhesus macaques that received estrogen replacement therapy showed fewer amyloid plaques than those that did not receive the hormone. This effect was observed regardless of the type of diet that the animals consumed. These findings suggest that hormone replacement might be a helpful treatment to consider for Alzheimer’s disease. Supported by ORIP (P51OD011092, R24OD011895, S10OD025002) and NIA.
Association of Age at Menopause and Hormone Therapy Use With Tau and β-Amyloid Positron Emission Tomography
Coughlan et al., JAMA Neurology. 2023.
https://pubmed.ncbi.nlm.nih.gov/37010830/
To understand the predominance (70%) of women among individuals with Alzheimer’s disease, the investigators studied regional tau and β-amyloid (Aβ) in relation to age at menopause and hormone therapy (HT) in postmenopausal women and age-matched men using positron emission tomography. The study demonstrated that females exhibited higher tau deposition compared with age-matched males, particularly in the setting of elevated Aβ; earlier age at menopause and late initiation of HT were associated with increased tau vulnerability. This study suggests female individuals with these conditions may be at higher risk of pathological burden. Supported by ORIP (S10OD025245), NIA, and NICHD.
Chronic TREM2 Activation Exacerbates Aβ-Associated Tau Seeding and Spreading
Jain et al., Journal of Experimental Medicine. 2023.
Using a mouse model for amyloidosis in which Alzheimer’s Disease (AD)–associated tau is injected into the brain to induce amyloid β (Aβ)–dependent tau seeding/spreading, investigators found that chronic administration of an activating triggering receptor expressed on myeloid cells 2 (TREM2) antibody increases microglial activation of dystrophic neurites surrounding Aβ plaques (NP) but increases NP-tau pathology and neuritic dystrophy without altering Aβ plaque burden. These data suggest that sustained microglial activation through TREM2 that does not result in strong myeloid removal might exacerbate Aβ-induced tau pathology, which could have important clinical implications. Supported by ORIP (S10OD021629) and NIA.