Biology subjects

the Alzheimers Disease Neuroimaging Initiative,

Publications and source records attributed to the Alzheimers Disease Neuroimaging Initiative,.

3 recordsLinked to original sources

bioRxiv2025

Harmonized Protocol for Subfield Segmentation in the Hippocampal Body on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically-valid, reliable, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI (http://www.hippocampalsubfields.com). Here, we report the first portion of the protocol focused on subfields in the hippocampal body; protocols for the head and tail are in development. The body protocol includes definitions of the internal boundaries between subiculum, Cornu Ammonis (CA) 1-3 subfields, and dentate gyrus, in addition to the external boundaries of the hippocampus apart from surrounding white matter and cerebrospinal fluid. The segmentation protocol is based on a novel histological reference data set labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. All boundary definitions were rated as having high clarity and reached consensus agreement by Delphi procedure. The harmonized body protocol yielded high inter- and intra-rater reliability. In the present paper we report the procedures to develop and test the protocol, as well as the detailed procedures for manual segmentation using the harmonized protocol. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in neurodegenerative diseases.

neuroscience↗

bioRxiv2019

Mitonuclear interactions influence Alzheimer’s disease risk

We examined the associations between mitochondrial DNA haplogroups (MT-hg) and their interactions with a polygenic risk score based on nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset of dementia (AOO). Logistic regression was used to determine the effect of MT-hgs and nMT-PRS on dementia at baseline (332 controls / 204 cases). Cox proportional hazards models were used to model dementia AOO (n=1047; 433 incident cases). Additionally, we tested for interactions between MT-hg and nMT-PRS in the logistic and Cox models. MT-hg K and a one SD larger nMT-PRS were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K and T were observed. Individual MT-hg were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T and a synergistic interaction between the nMT-PRS and MT-hg V. These results suggest that MT-hgs influence dementia risk, and that variants in the nuclear and mitochondrial genome interact to influence the age of onset of dementia.\n\nHighlightsO_LIMitochondrial dysfunction has been proposed to influence dementia risk\nC_LIO_LIMT-hg K and T interacted with a genetic risk score to reduce dementia risk\nC_LIO_LIMT-hg T and V interacted with a genetic risk score to influence dementia age of onset\nC_LI

genetics↗

bioRxiv2018

A systematic bias in DTI findings

Diffusion tensor imaging (DTI) has been extensively used to map changes in brain tissue related to neurological disorders. Among the most widespread DTI findings are increased mean diffusivity and decreased fractional anisotropy of white matter tissue in neurodegenerative diseases. Here we utilize multi-shell diffusion imaging to separate diffusion signal of the brain parenchyma from fluid within the white matter. We show that unincorporated anisotropic water in perivascular space (PVS) significantly, and systematically, biases DTI measures, casting new light on the biological validity of many previously reported findings. Despite the challenge this poses for interpreting these past findings, our results suggest that multi-shell diffusion MRI provides a new opportunity for incorporating the PVS contribution, ultimately strengthening the clinical and scientific value of diffusion MRI.\n\nHighlightsO_LIPerivascular space (PVS) fluid significantly contributes to diffusion tensor imaging metrics\nC_LIO_LIIncreased PVS fluid results in increased mean diffusivity and decreased fractional anisotropy\nC_LIO_LIPVS contribution to diffusion signal is overlooked and demands further investigation\nC_LI

neuroscience↗