Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).
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http://dx.doi.org/10.1523/JNEUROSCI.3113-13.2014 | DOI Listing |
Alzheimers Dement
December 2024
The Second Affiliated Hospital of Chongqing Medical University, Chongqing, Chong Qing, China.
Background: Alzheimer's disease (AD) frequently coexists with cerebral small vessel disease (CSVD) is common in the aging population, yet the underlying mechanisms are not yet fully understood. Both long-term blood pressure variability (BPV) and plasma neurofilament light (PNFL) were identified as potential biomarkers for AD and CSVD. This study aims to understand the mechanisms of comorbidity between AD and CSVD by investigating the associations among BPV, PNFL, and comorbidity.
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December 2024
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Background: White matter hyperintensities (WMH) are commonly observed on MRI in Alzheimer's disease (AD), but the molecular pathways underlying their relationships with the ATN biomarkers remain unclear. The aim of this study was to identify genetic variants that may modify the relationship between WMH and the ATN biomarkers.
Method: This genome-wide interaction study (GWIS) included individuals with AD, MCI, and normal cognition from ADNI (n = 1012).
Alzheimers Dement
December 2024
The Second Affiliated Hospital of Chongqing Medical University, Chongqing, Chong Qing, China.
Background: The mesolimbic system plays a crucial role in weight regulation and cognition. Previous studies suggest that the pathology of Alzheimer's disease (AD) can lead to the atrophy of the mesolimbic system and body mass index (BMI) decline. It remains unknown whether BMI is associated with the the mesolimbic system in AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) denotes TDP-43 deposition in older age and is consequential for cognitive function. Currently there is no way to identify LATE-NC during life. Some forms of TDP-43 deposition in younger age, related to frontotemporal dementia (FTD), are associated with pronounced asymmetrical atrophy of the temporal lobe.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Mayo Clinic Florida, Jacksonville, FL, USA.
Background: We previously identified the novel mechanism of pathological tau transfer via extracellular vesicles (EVs) in Alzheimer's disease (AD). Targeting EV secretion to mitigate tau transfer is therefore a promising therapeutic approach for AD. P2X purinoreceptor 7 (P2RX7), an ATP-gated cationic channel, regulates microvesicle shedding or secretion of multivesicular body-derived exosomes.
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