Amino acid profiling could expedite tailored dementia interventions: Analysis

By Nicola Gordon-Seymour

- Last updated on GMT

© coffeekai / Getty Images
© coffeekai / Getty Images

Related tags Amino acid Mild cognitive impairment Brain health

Measuring plasma free amino acids (PFAA) may have importance in assessing the risk of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI) and facilitate a lifestyle approach to dementia management, according to the authors of a report published in Frontiers in Nutrition.

Nutritional epidemiological studies demonstrate the importance of protein intake to maintain brain function in the elderly, while lower amino acid scores are associated with cognitive impairment.

Pharmacotherapy is currently used to delay cognitive impairment among the elderly – to prevent accumulation of amyloid-B (AB), for example - but is “economically challenging”​ in the long-term, therefore lifestyle interventions are posited as a realistic option to address dementia, the authors said.

“Low-protein diets have been reported to decrease essential amino acid influx to the brain and cause inflammation in the brain, which may be one of the contributing factors of dementia​.

“From this perspective, a lifestyle modification approach is one of the realistic options. When considered in relation to body mass index (BMI), low BMI is a clear risk factor for AD in elderly individuals.”

Suitable indicator

Identifying precision biomarkers is key to providing tailored treatment based on a patient’s biological and nutritional status, the authors commented.

“When considering nutritional interventions based on the current results, the molecular mechanism that links circulating EAAs and development of dementia is important.”

The interim follow-up analysis of 352 MCI patients aimed to determine the relationship between PFAA and AD progression. It found lower plasma concentrations of all nine essential amino acids (EAA) in AD-converts and suggests PFAA profile is an independent risk factor for AD development.

“It is known that some individuals with MCI convert to AD, while others do not, and it is intriguing that these differences are reflected in the differences in plasma BCAA and His concentrations. Our study indicates that PFAA may be a suitable indicator,” ​said the authors.

Analysis design

MCI longitudinal study patients were recruited from 14 Japanese medical institutions and 220 control (CN) participants from communities in four cities and one medical centre.

Inclusion criteria was age (50 years or over), no dementia diagnosis, living independently, MMSE score of 24 points or higher, and no depression.

Baseline blood samples were collected under fasting conditions and tested for 22 amino acids. BMI was calculated based on height and weight and blood parameters measured.

Apolipoprotein (APOE) genotypes (a risk factor for dementia) were determined using TaqMan PCR Assays. Participants with one or two alleles of APOE E4 were assigned to the positive group and those without the allele to the negative group.

At two-year follow-up, MCI participants was assessed for cognitive function (AD or MCI). Those who remained with MCI or reverted to CN were categorised as MCI-stable, and participants who developed AD were categorised to the AD-convert group.

Summary results

AD patients also demonstrated lower concentrations of three branched-chain amino acids (BCAA) – valine (Val), leucine (Leu), and isoleucine (Ile) – and histidine (His) and received lower mini-mental state examination (MMSE) scores.

Concentrations of plasma methionine (Met), Val, Leu, and His were lower in the AD group when compared to the control (CN) group, but there was no difference between CN and MCI-stable patients. Conversely, lysine (Lys) was lower in both AD-converted and MCI-stable groups than the CN.

The difference in APOE E4 possession showed various strengths of association. In the negative group, the difference in three BCAA concentrations between MCI-stable and AD-converted groups was statistically significant but not in the positive group.

Moreover, differences in His, glycine (Gly) and Glu between MCI-stable and AD-converted groups were greater in the APOE E4 negative group, compared with the positive.

“The concentration of BCAAs in the blood might reflect AD pathology other than Ab or taurine (tau) accumulation, such as inflammation or oxidative stress in the brain,” ​the authors’ commented.

“Compared to Lys and threonine (Thr), which are commonly decreased in MCI compared to CN participants, circulating BCAAs and His may be related to pathological conditions and/or nutritional status, and future detailed studies are warranted.”

Source: Frontiers inNutrition
Published online, December 14, 2022:
‘Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment’
Authors: T. Ikeuchi, et al.

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