Data Sheet 1_Aluminium neurotoxicity beyond the brain: a mechanistic systematic review of autonomic and peripheral dysfunction.doc

Synthesis of the evidence reveals a consistent “Barrier-Stress Axis.” Mechanistically, Al targets tight junction proteins (e.g., occludin, claudin-5) in the blood-brain and blood-nerve barriers, leading to oxidative stress in the nucleus tractus solitarius and peripheral nerves. Clinically, this manifests as reduced heart rate variability (HRV) and impaired baroreflex sensitivity in both occupational human cohorts and experimental rat models.

While peripheral nerve conduction changes are noted, human data remain limited by small sample sizes and confounding environmental factors. Preliminary evidence suggests that ANS and PNS dysregulation may precede overt cognitive decline in Al toxicity. HRV and baroreflex sensitivity are promising candidates for early-stage screening.

However, these findings should currently be viewed as hypothesis-generating; longitudinal human studies are required to validate these markers and control for occupational co-exposures.</p>