Advances at the intersection of normal brain aging and Alzheimer’s disease

2017 ◽  
Vol 322 ◽  
pp. 187-190 ◽  
Author(s):  
Sarah M. Neuner ◽  
Lynda A. Wilmott ◽  
Corina Burger ◽  
Catherine C. Kaczorowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Aging ◽  
Normal Brain

scholarly journals Transcriptomic Changes Highly Similar to Alzheimer’s Disease Are Observed in a Subpopulation of Individuals During Normal Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-Vianney Haure-Mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Normal Aging ◽  
Aging Brain ◽  
Normal Brain ◽  
Older Individuals ◽  
Cognitively Normal

Aging is a major risk factor for late-onset Alzheimer’s disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examined multiple large-scale transcriptomic datasets from both normal aging and LOAD brains to understand the molecular interconnection between aging and LOAD. We found that shared gene expression changes between aging and LOAD are mostly seen in the hippocampal and several cortical regions. In the hippocampus, the expression of phosphoprotein, alternative splicing and cytoskeleton genes are commonly changed in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are more related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also found that normal aging brain transcriptomes from relatively young donors (45–70 years old) clustered into several subgroups and some subgroups showed gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptomic datasets from another cohort of older individuals (>70 years), we found that samples from cognitively normal older individuals clustered with the “healthy aging” subgroup while AD samples mainly clustered with the “AD similar” subgroups. This may imply that individuals in the healthy aging subgroup will likely remain cognitively normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitively normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the “normal brain aging” to identify the very early molecular events that may lead to LOAD development.

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.

Elevated oxidative stress in models of normal brain aging and Alzheimer's disease

Life Sciences ◽  
1999 ◽  
Vol 65 (18-19) ◽  
pp. 1883-1892 ◽  
Author(s):  
D.Allan Butterfield ◽  
Beverly Howard ◽  
Servet Yatin ◽  
Tanuja Koppal ◽  
Jennifer Drake ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Aging ◽  
Normal Brain

scholarly journals Transcriptomic changes highly similar to Alzheimer's disease are observed in a subpopulation of individuals during normal brain aging

2021 ◽  
Author(s):  
Shouneng Peng ◽  
Lu Zeng ◽  
Jean-vianney Haure-mirande ◽  
Minghui Wang ◽  
Derek M. Huffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Healthy Aging ◽  
Brain Aging ◽  
Late Onset ◽  
Normal Aging ◽  
Normal Brain ◽  
Older Individuals

Aging is a major risk factor for late-onset Alzheimer's disease (LOAD). How aging contributes to the development of LOAD remains elusive. In this study, we examine multiple large-scale human brain transcriptomic data from both normal aging and LOAD to understand the molecular interconnection between aging and LOAD. We find that shared gene expression changes between aging and LOAD are mostly seen in the hippocampus and several cortical regions. In the hippocampus, phosphoprotein, alternative splicing and cytoskeleton are the commonly dysregulated biological pathways in both aging and AD, while synapse, ion transport, and synaptic vesicle genes are commonly down-regulated. Aging-specific changes are associated with acetylation and methylation, while LOAD-specific changes are related to glycoprotein (both up- and down-regulations), inflammatory response (up-regulation), myelin sheath and lipoprotein (down-regulation). We also find that normal aging brains from relatively young donors (45-70 years old) cluster into subgroups and some subgroups show gene expression changes highly similar to those seen in LOAD brains. Using brain transcriptome data from older individuals (>70 years), we find that samples from cognitive normal older individuals cluster with the "healthy aging" subgroup while AD samples mainly cluster with the AD similar subgroups. This implies that individuals in the healthy aging subgroup will likely remain cognitive normal when they become older and vice versa. In summary, our results suggest that on the transcriptome level, aging and LOAD have strong interconnections in some brain regions in a subpopulation of cognitive normal aging individuals. This supports the theory that the initiation of LOAD occurs decades earlier than the manifestation of clinical phenotype and it may be essential to closely study the "normal brain aging" in a subgroup of individuals in their 40s-60s to identify the very early events in LOAD development.

Normal brain aging and Alzheimer's disease are associated with lower cerebral pH: an in vivo histidine 1H-MR spectroscopy study

2020 ◽  
Vol 87 ◽  
pp. 60-69 ◽  
Author(s):  
Epameinondas Lyros ◽  
Andreas Ragoschke-Schumm ◽  
Panagiotis Kostopoulos ◽  
Alexandra Sehr ◽  
Martin Backens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mr Spectroscopy ◽  
Brain Aging ◽  
Normal Brain ◽  
Spectroscopy Study ◽  
1H Mr Spectroscopy
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