Formaldehyde toxicity in age-related neurological dementia

The primordial small gaseous molecules, such as: NO, CO, H2S and formaldehyde (FA) are present in the brains. Whether FA as well as the other molecules participates in brain functions is unclear. Recently, its pathophysiological functions have been investigated. Notably, under physiological conditions, learning activity induces a transient generation of hippocampal FA, which promotes memory formation by enhancing N-methyl-D-aspartate (NMDA)-currents. However, ageing leads to FA accumulation in brain for the dysregulation of FA metabolism; and excessive FA directly impairs memory by inhibiting NMDA-receptor. Especially, in Alzheimer's disease (AD), amyloid-beta (A beta) accelerates FA accumulation by inactivating alcohol dehydrogenase-5; in turn, FA promotes A beta oligomerization, fibrillation and tau hyperphosphorylation. Hence, there is a vicious circle encompassing A beta assembly and FA generation. Even worse, FA induces A beta deposition in the extracellular space (ECS), which blocks the medicines (dissolved in the interstitial fluid) flowing into the damaged neurons in the deep cortex. However, phototherapy destroys A beta deposits in the ECS and restores ISF flow. Coenzyme Q10, which scavenges FA, was shown to ameliorate A beta-induced AD pathological phenotypes, thus suggesting a causative relation between FA toxicity and AD. These findings suggest that the combination of these two methods is a promising strategy for treating AD.

Automated summary

Research suggests that the accumulation of formaldehyde (FA) in the brain may have a negative impact on cognitive function, especially in aging and Alzheimer's disease progression. Additionally, there is a vicious circle between the deposition of amyloid-beta (A beta) and the generation of FA, accelerating the progression of the disease.