P2-118: Puzzle: Why is the Exponential Increase in Age-Specific Prevalence of Alzheimer’s Disease (AD) not Paralleled by the Prevalence Curve for AD Brain Lesions at Autopsy? Observations from the Nun Study (NS) and Honolulu-Asia Aging Study (HAAS)

Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies. Methods: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Conclusion: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.

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Linguistic Ability in Early Life and the Neuropathology of Alzheimer's Disease and Cerebrovascular Disease: Findings from the Nun Study

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2000.tb06347.x ◽

2000 ◽

Vol 903 (1 VASCULAR FACT) ◽

pp. 34-38 ◽

Cited By ~ 79

Author(s):

D. A. SNOWDON ◽

L. H. GREINER ◽

W. R. MARKESBERY

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrovascular Disease ◽

Early Life ◽

Linguistic Ability ◽

Nun Study

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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽

10.3390/cells10113261 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3261

Author(s):

Xiao Liu ◽

Qian Zhou ◽

Jia-He Zhang ◽

Xiaoying Wang ◽

Xiumei Gao ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Stage ◽

Disease Model ◽

Amyloid Β ◽

Brain Lesions ◽

Synaptic Dysfunction ◽

Synaptic Loss ◽

And Function ◽

The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

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