Intrinsic programs shape brain maturation; however, which of these programs are perturbed by prematurity as well as the molecular pathways involved remain unknown. The human cerebellum serves as a paradigm of extrauterine development—its accelerated growth and circuit formation align with the third trimester, a period disrupted by preterm delivery. Using multimodal datasets encompassing in vivo neuroimaging and neurodevelopmental outcomes with postmortem spatial-transcriptomic and histopathological profiling, we show that prematurity diverts the cerebellar developmental trajectory. Cerebellar growth and functional outcomes scaled with gestational age, despite modifying perinatal exposures. Spatially resolved developmental programs underlying macroscopic trajectories were marked by incomplete granule cell maturation and impaired Purkinje cell structural refinement, which indicate lineage-specific developmental asynchrony. Thus, prematurity constitutes biologically displaced maturation, in which infants of equivalent postmenstrual age occupy divergent developmental states.

We conducted a systematic review and meta-analysis of associations between apolipoprotein E (APOE) alleles and frontotemporal lobar degeneration (FTLD)-spectrum disorders. MEDLINE, Embase, CENTRAL, and Google Scholar were searched. APOE2 and APOE4 carrier status were compared between FTLD-spectrum disorders and healthy controls (HCs) or individuals with Alzheimer’s disease (AD). Forty studies were included. APOE4 carriage was more frequent in frontotemporal dementia (FTD) compared with HC (OR = 1.72; 95% CI = 1.45–2.04) and less common than in AD (OR = 0.35; 95% CI = 0.29–0.42). In contrast, APOE2 carriage was less prevalent in FTD relative to HC (OR = 0.83; 95% CI = 0.70–0.98) but more frequent compared with AD (OR = 1.80; 95% CI = 1.29–2.52). APOE4 effects were most pronounced in behavioral variant FTD. In clinically confirmed progressive supranuclear palsy (PSP), APOE4 carriage was not associated with PSP. Analysis restricted to pathologically confirmed PSP cases, however, showed lower APOE4 carriage in PSP than in healthy controls (OR = 0.78, 95% CI = 0.65–0.94), although this association failed to reach the multiplicity-adjusted significance threshold. APOE2 carriage was not associated with PSP in either clinically established or pathologically confirmed samples. Evidence was insufficient to establish or exclude associations for other FTLD-spectrum disorders because of the limited available data. In conclusion, APOE alleles show distinct associations across the FTLD spectrum.