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In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy. [ABSTRACT FROM AUTHOR]