Alzheimer’s Nemesis

Ill-understood and highly stigmatized, Alzheimer’s disease is a life-limiting illness marked by a gradual deterioration of one’s cognitive abilities like memory, thinking, and the ability to perform daily activities. While plaques clustering around the brain cells are understood to be the culprit, therapies targeted at clearing them have come to a dead end. Spotting the metabolic dysfunction long ahead of the onset of the disease, the School of Life Sciences research team led by Prof. Kim Chow has shone light on a promising cure—which is as simple as food supplements.

The spiralling down starts with a genetic variation within the gene LRP6. This tiny change leads to the diminishing of the gene itself in the forebrain, as shown by adult mice, and the latter’s cognitive and memory functions are dramatically impaired. The mutated gene further triggers an extensive reprogramming in cerebral metabolism, as its major carriers—large star-shaped cells called astrocytes—are forced to take up glutamine and branched chain amino acids, both essential for neurotransmission, instead of glucose as their fuel in the absence of the LRP6 function. As the metabolic substitution becomes chronic, it would finally take its toll on neurotransmission, hampering memory and thinking.

The team also made another finding regarding the genetic variant of the APOE-E4 allele, the commonest risk factor of Alzheimer’s with 6.3–9.3% frequency in Asian populations. The allele’s protein product can trap LRP6 inside the cell, keeping it away from the cell surface where it functions.

At any rate, the recasting of Alzheimer’s as a pervasive metabolic disorder that takes place way before the symptoms develop has lent insight into its mitigation and treatment, which go by the simple way of direct supplement of glutamine and branched chain amino acids to the brain. Proved effective in other clinical settings, the vital amino acids can be consumed prodigiously without adverse effects, and with huge benefits.