Brain gamma-aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer's disease

Abstract

Activities of Gamma-aminobutyrate aminotransferase (GABA-T) and Monoamine oxidase (MAO)-A and -B were estimated in postmortem brains from 6 control subjects without psychiatric or neurologic disorders and 8 histopathologically verified cases of patients with Alzheimer's disease and senile dementia of Alzheimer type (AD/SDAT). The enzyme activities were examined in four cortical brain regions, three nuclei in the basal ganglia, thalamus and white matter. GABA-T activities in the cortical regions (frontal, parietal, occipital and temporal cortices) and nucleus caudatus were significantly lowered in the AD/SDAT patients. The MAO-A activities were significantly increased in the occipital cortex, caudate nucleus, thalamus and white matter in the AD/SDAT patients. No significant differences were found in the other regions (frontal cortex, parietal cortex, temporal cortex, putamen and globus pallidus). The MAO-B activities in three cortical regions (frontal, parietal and occipital cortices), thalamus and white matter were significantly increased in the AD/SDAT patients, whereas no difference was apparent in the other regions. The changed activities could not be correlated with age or postmortem time. The present results are the first describing decreased GABA-T activities as well as increased MAO-A activities in brain from patients with AD/SDAT, while the results with MAO-B support previous findings. A possible connection was found between the order of magnitude of the changes in enzyme activities and the severity of the disease.

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

“…The MAO-B increase could be due to the local infiltration of glial cells in these areas as MAO-B is mainly expressed in this cell type, a significant proportion of which are found in the proximity of -amyloid plaques (a hallmark of AD pathology) [32,88,94]. MAO-A activity and MAO-A mRNA are also reported to be elevated in several areas of the AD brain including the occipital cortex, frontal lobe of neocortex, parietal cortex, and locus coeruleus [93,95,96] as well as in the caudate nucleus, thalamus and white matter [97]. Although there are also reports of decreases in MAO-A activity in AD brains [95,98], it is important to realize that a substantial amount of MAO-A (i.e.…”

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

“…Studies have shown that activated MAO in the brains of patients with AD is a biomarker for AD (35)(36)(37). This was demonstrated by [ 11 C]-L-deprenyl using whole hemisphere autoradiography (38)(39)(40), epidemiology (41,42), morphology (43), as well as single-photon emission computed tomography (44).…”

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

“…With age, the concentration of MAO-B in the brain increases (Oreland & Gottfries, 1986). A number of studies in patients with AD have shown that up-regulated MAO is a reasonable biomarker for the disease (Sparks, Woeltz, & Markesbery, 1991;Oreland & Gottfries, 1986;Sherif, Gottfries, Alafuzoff, & Oreland, 1992) with levels significantly up-regulated to as much as 30% (Zellner et al, 2012). Such elevated and up-regulated levels of MAO may contribute to the oxidative stress and cognitive impairment through neuroinflammation as MAO generates hydrogenperoxide and ammonia which are among the main culprits contributing to the formation of amyloid plaques (Huang et al, 2012;Zheng, Fridkin, & Youdim, 2012).…”