scholarly journals Women's brain aging: Effects of sex‐hormone exposure, pregnancies, and genetic risk for Alzheimer's disease

2020 ◽  
Vol 41 (18) ◽  
pp. 5141-5150 ◽  
Author(s):  
Ann‐Marie G. Lange ◽  
Claudia Barth ◽  
Tobias Kaufmann ◽  
Ivan I. Maximov ◽  
Dennis Meer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Brain Aging ◽  
Sex Hormone ◽  
Aging Effects ◽  
Hormone Exposure

scholarly journals Women’s brain aging: effects of sex-hormone exposure, pregnancies, and genetic risk for Alzheimer’s disease

2019 ◽  
Author(s):  
Ann-Marie G. de Lange ◽  
Claudia Barth ◽  
Tobias Kaufmann ◽  
Ivan I. Maximov ◽  
Dennis van der Meer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Hormones ◽  
Genetic Risk ◽  
Brain Aging ◽  
Sex Hormone ◽  
Cumulative Exposure ◽  
Normal Brain ◽  
Aging Effects ◽  
Hormone Exposure

AbstractSex hormones such as estrogen fluctuate across the female lifespan, with high levels during reproductive years and natural decline during the transition to menopause. Women’s exposure to estrogen may influence their heightened risk of Alzheimer’s disease (AD) relative to men, but little is known about how it affects normal brain aging. Recent findings from the UK Biobank demonstrate less apparent brain aging in women with a history of multiple childbirths, highlighting a potential link between sex-hormone exposure and brain aging. We investigated endogenous and exogenous sex-hormone exposure, genetic risk for AD, and neuroimaging-derived biomarkers for brain aging in 16,854 middle to older-aged women. The results showed that as opposed to parity, higher cumulative sex-hormone exposure was associated with more evident brain aging, indicating that i) high levels of cumulative exposure to sex-hormones may have adverse effects on the brain, and ii) beneficial effects of pregnancies on the female brain are not solely attributable to modulations in sex-hormone exposure. In addition, for women using hormonal replacement therapy (HRT), starting treatment earlier was associated with less evident brain aging, but only in women with a genetic risk for AD. Genetic factors may thus contribute to how timing of HRT initiation influences women’s brain aging trajectories.

scholarly journals Sex differences in brain aging among adults with family history of Alzheimer’s disease and APOE4 genetic risk

2021 ◽  
Vol 30 ◽  
pp. 102620
Author(s):  
Sivaniya Subramaniapillai ◽  
Sricharana Rajagopal ◽  
Jamie Snytte ◽  
A. Ross Otto ◽  
Gillian Einstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Family History ◽  
Genetic Risk ◽  
Brain Aging ◽  
History Of

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

scholarly journals Interaction of Alzheimer’s Disease-Associated Genetic Risk with Indicators of Socioeconomic Position on Mild Cognitive Impairment in the Heinz Nixdorf Recall Study

2021 ◽  
pp. 1-11
Author(s):  
Mirjam Frank ◽  
Jonas Hensel ◽  
Lisa Baak ◽  
Sara Schramm ◽  
Nico Dragano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Socioeconomic Position ◽  
Genetic Risk ◽  
Late Onset ◽  
Heinz Nixdorf Recall Study ◽  
Low Education ◽  
Additive Scale

Background: The apolipoprotein E (APOE) ɛ4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. Objective: To investigate whether APOE ɛ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. Methods: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOE ɛ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. Results: Indication for interaction on the additive scale was found between APOE ɛ4 and low education on MCI (RERI: 0.52 [95% -confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOE ɛ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% -CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% -CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. Conclusion: Results indicate that low education may have an impact on APOE ɛ4 expression on MCI, especially among women.

scholarly journals Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease

2019 ◽  
Vol 10 (2) ◽  
pp. 470 ◽  
Author(s):  
Ashok K. Shetty ◽  
Raghavendra Upadhya ◽  
Leelavathi N. Madhu ◽  
Maheedhar Kodali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Brain Aging ◽  
Lateral Sclerosis

scholarly journals Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis

2015 ◽  
Vol 112 (38) ◽  
pp. 11965-11970 ◽  
Author(s):  
Li Zhu ◽  
Minghao Zhong ◽  
Gregory A. Elder ◽  
Mary Sano ◽  
David M. Holtzman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Genetic Risk ◽  
Primary Neurons ◽  
Loss Of Function ◽  
Sporadic Alzheimer’S Disease ◽  
Postmortem Human Brain ◽  
Apoe4 Allele ◽  
Synaptojanin 1

The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer’s disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

scholarly journals Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease

Brain ◽  
2006 ◽  
Vol 129 (11) ◽  
pp. 2984-2991 ◽  
Author(s):  
N. Brouwers ◽  
K. Sleegers ◽  
S. Engelborghs ◽  
V. Bogaerts ◽  
S. Serneels ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Genetic Risk ◽  
Precursor Protein
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