Carriers of the so-called ‘Alzheimer’s gene’ (apoE4) comprise 65% of all Alzheimer's cases. A new study helps us understand why that’s true. Genetically engineered mice reveal that apoE4 is associated with the loss of GABAergic interneurons in the hippocampus. This is consistent with low levels of GABA (produced by these neurons) typically found in Alzheimer’s brains. This loss was associated with cognitive impairment in the absence of amyloid beta accumulation, demonstrating it is an independent factor in the development of this disease.

The relationship with the other major characteristic of the Alzheimer’s brain, tau tangles, was not independent. When the mice’s tau protein was genetically eliminated, the mice stopped losing GABAergic interneurons, and did not develop cognitive deficits. Previous research has shown that suppressing tau protein can also prevent amyloid beta from causing memory deficits.

Excitingly, daily injections of pentobarbital, a compound that enhances GABA action, restored cognitive function in the mice.

The findings suggest that increasing GABA signaling and reducing tau are potential strategies to treat or prevent apoE4-related Alzheimer's disease.

Analysis of DNA and lifestyle data from a representative group of 2,500 U.S. middle- and high-school students tracked from 1994 to 2008 in the National Longitudinal Study of Adolescent Health has revealed that lower academic performance was associated with three dopamine gene variants. Having more of the dopamine gene variants (three rather than one, say) was associated with a significantly lower GPA.

Moreover, each of the dopamine genes (on its own) was linked to specific deficits: there was a marginally significant negative effect on English grades for students with a specific variant in the DAT1 gene, but no apparent effect on math, history or science; a specific variant in the DRD2 gene was correlated with a markedly negative effect on grades in all four subjects; those with the deleterious DRD4 variant had significantly lower grades in English and math, but only marginally lower grades in history and science.

Precisely why these specific genes might impact academic performance isn’t known with any surety, but they have previously been linked to such factors as adolescent delinquency, working memory, intelligence and cognitive abilities, and ADHD, among others.

It’s been suggested before that Down syndrome and Alzheimer's are connected. Similarly, there has been evidence for connections between diabetes and Alzheimer’s, and cardiovascular disease and Alzheimer’s. Now new evidence shows that all of these share a common disease mechanism. According to animal and cell-culture studies, it seems all Alzheimer's disease patients harbor some cells with three copies of chromosome 21, known as trisomy 21, instead of the usual two. Trisomy 21 is characteristic of all the cells in people with Down syndrome. By age 30 to 40, all people with Down syndrome develop the same brain pathology seen in Alzheimer's. It now appears that amyloid protein is interfering with the microtubule transport system inside cells, essentially creating holes in the roads that move everything, including chromosomes, around inside the cells. Incorrect transportation of chromosomes when cells divide produces new cells with the wrong number of chromosomes and an abnormal assortment of genes. The beta amyloid gene is on chromosome 21; thus, having three copies produces extra beta amyloid. The damage to the microtubule network also interferes with the receptor needed to pull low-density lipoprotein (LDL — the ‘bad’ cholesterol) out of circulation, thus (probably) allowing bad cholesterol to build up (note that the ‘Alzheimer’s gene’ governs the low-density lipoprotein receptor). It is also likely that insulin receptors are unable to function properly, leading to diabetes.

A brain scanning study using Pittsburgh Compound B, involving 42 healthy individuals (aged 50-80), of whom 14 had mothers who developed Alzheimer's, 14 had fathers with Alzheimer's, and 14 had no family history of the disease, has found that those with a maternal history had 15% more amyloid-beta plaques than those with a paternal history, and 20% more than those with no family history. The findings add to evidence that having a mother with Alzheimer’s is a greater risk factor than having a father with Alzheimer’s. The groups did not differ in age, gender, education, or apolipoprotein E (ApoE) status.

Another gene has been identified that appears to increase risk of Alzheimer’s. The gene, MTHFD1L, is located on chromosome six. Comparison of the genomes of 2,269 people with late-onset Alzheimer's disease and 3,107 people without the disease found those with a particular variation in this gene were almost twice as likely to develop Alzheimer's disease as those people without the variation. The gene is involved in influencing the body's levels of homocysteine (high levels are known to be a strong risk factor), and have also been implicated in coronary artery disease.