The role of neuroinflammation in the connections between autism spectrum disorder and Alzheimer's disease and related dementias: A review

Recent evidence suggests a link between autism spectrum disorder (ASD) and early-onset Alzheimer's disease and related dementias (AD/ADRD), yet the mechanisms underlying this association remain poorly understood. This narrative review investigates whether early management of ASD may reduce the risk of developing AD/ADRD by targeting shared biological pathways. A literature search was conducted using PubMed and included English-language studies published from 1996 to 2026. Eligible studies addressed ASD, AD/ADRD, neuroinflammation, aging, or dementia, and included systematic reviews, meta-analyses, narrative reviews, clinical trials, randomized controlled trials, and translational animal studies. Studies lacking discussion of mechanisms relevant to ASD, neuroinflammation, aging, or dementia were excluded. Search terms included AD, dementia, ASD, inflammation, pregnenolone, omega-3, prednisolone, celecoxib, minocycline, N-acetylcysteine, sulforaphane, histamine receptor agonists, and GABA. Additional studies were identified through reference list screening. Of 170 records identified, 133 met the inclusion criteria and formed the basis for the review. Findings indicate that neuroinflammation is a central mechanism linking ASD-related comorbidities with established AD/ADRD risk factors. The evidence suggests that reducing neuroinflammation, particularly through interventions targeting microglial activation during childhood or early adulthood, may lower the likelihood of early-onset AD/ADRD in individuals with ASD. Although current evidence is primarily theoretical and indirect, it supports further investigation of anti-inflammatory strategies as potential preventive interventions. The review concludes by proposing future empirical studies to test whether early neuroinflammation-targeted treatment in ASD can reduce the incidence of early-onset AD/ADRD.