Cellular correlates of cortical thinning throughout the lifespan

Abstract

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

The trajectory of cortical GABA across the lifespan, an individual participant data meta-analysis of edited MRS studies

“…This may be due to the absence of clear hypotheses regarding Glx and a mechanistic focus on GABA, or simple omission of these data. Furthermore, it would be important to link these findings to anatomical measures underlying the different neurochemical measures, such as evidence of non-linear cortical thinning and histological studies of GABAergic neurons ( Pandya et al, 2019 ; Vidal-Pineiro et al, 2020 ).…”

Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD

“…We note that our justifications for selecting these areas for study were prior associations between PTSD, cortical thickness, and connectivity in these cortical areas ( Reuveni et al, 2016 ; Sadeh et al, 2016 ; Miller et al, 2015 ; Holmes et al, 2018 ). It is possible that these gene expression differences are related to or contribute to these structural associations, as myelination has been linked to connectivity ( Hunt et al, 2016 ), and cortical thinning has been linked to reduced proportions of several cell types including microglial cells ( Vidal-Pineiro et al, 2020 ). However, more work is needed to directly link the observed associations to specific neuropathological and imaging findings.…”

A Practical Guide to Sparse k-Means Clustering for Studying Molecular Development of the Human Brain

“…For example, many imaging studies reference synaptic development measurements ( Huttenlocher and Dabholkar, 1997 ) to account for rapid changes in cerebral cortex MRI signals during the first few years of life. More recently, gene expression databases have been used to identify candidate cellular and molecular features, such as those underlying cortical thinning throughout the life-span ( Vidal-Pineiro et al, 2020 ) or testosterone-related structural properties of the adolescent cerebral cortex ( Liao et al, 2021 ). However, the rare and valuable nature of human postmortem brain samples means that gene expression studies have small sample sizes, especially compared to modern MRI studies that use a population neuroscience approach and aggregate data from hundreds or thousands of subjects ( Paus, 2016 ).…”