Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer’s disease subgroups

• DOI: 10.1016/j.nicl.2021.102660
• Publication Date: 2021-04-04T00:10:42Z
• Authors: Colin Groot; Michel J. Grothe; Shubhabrata Mukhe...; Irina Jelistratova; Iris Jansen; Anna Catharina va...; Shannon L. Risacher; Andrew J. Saykin; Christine L. Mac ...; Jesse Mez; Emily H. Trittschuh; Gregor Gryglewski; Rupert Lanzenberger; Yolande A.L. Pijn...; Frederik Barkhof; Philip Scheltens; Wiesje M. van der...; Paul K. Crane; Rik Ossenkoppele
• Keywords: Clinical Dementia Rating

The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups amyloid-β positive clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 5). All participants underwent neuropsychological assessment tests covering memory, executive-functioning, language visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment to intra-individual average domains, yielded following in our sample; AD-Memory (n = 41), AD-Executive 117), AD-Language 33), AD-Visuospatial 171). We performed voxel-wise contrasts GM derived from 3Tesla structural MRI controls 127, age 58 9, 42% MMSE 29 1), observed differences closely matched respective profiles. Specifically, detected lower medial temporal lobe AD-Memory, fronto-parietal AD-Executive, asymmetric (left < right) AD-Language, posterior areas AD-Visuospatial. In order examine possible biological drivers these volumes, correlated subgroup-specific brain-wide based on stereotactic characterization transcriptional architecture human brain as provided by Allen atlas. Gene-set enrichment analyses revealed variations genes involved processes like mitochondrial respiration metabolism proteins were patterns volume multiple subgroups. Other vs volume-associations only particular subgroups, e.g., cell cycle for specific sets related protein modification conclude show differences, distinct pathways may be emergence differences.