Alzheimer's Disease and Parkinson's Disease May Result from Reactivation of Embryologic Pathways Silenced at Birth.

Abstract

Alzheimer's disease (AD), Lewy Body Dementia (LBD), and Parkinson's disease (PD) form a continuum that may explain multiple aspects of age-related neurodegeneration. Inflammaging, the long-term result of the chronic physiological stimulation of the innate immune system, is integral to this process. The gut microbiome plays an important role in inflammaging, as it can release inflammatory products and communicate with other organs and systems. Although AD and PD are molecularly and clinically distinct disorders, their causes appear to underlie LBD. All three conditions lie on a continuum related to AD, PD, or LBD in vulnerable persons. Inflammation in AD is linked to cytokines and growth factors. Moreover, cytokines and neurotrophins profoundly affect PD and LBD. Growth factors, neurotrophins and cytokines are also involved in embryo neural development. Cytokines influence gene expression, metabolism, cell stress, and apoptosis in the preimplantation embryo. The responsible genes are silenced around birth. But if activated by inflammaging and viruses in the brain decades later, they could destroy the same neural structures they created in utero. For this reason, the pathology and progression of AD, LBD, and PD would be unique. Embryonic reactivation could explain two well documented features of AD. 1) NSAIDs reduce AD risk but fail as a treatment. 2) NSAIDs reduce AD risk because they suppress inflammaging. But they are not a treatment because they cannot silence the embryonic genes that have become active and damage the brain.