Investigators Connect Liver Function with Alzheimer Symptoms

Kwangsik Nho, PhD

An examination of how liver function relates to the development of Alzheimer disease (AD) shows how lower levels of alanine aminotransferase (ALT) is tied to AD biomarkers.

A team led by Kwangsik Nho, PhD, from the Indiana University School of Medicine, have reviewed cohort studies involving 1581 older adults with elevated asparate aminotransferase (AST) to ALT ratios and discovered consistent associations of serum-based liver function markers with AD biomarkers indicate the involvement of metabolic disturbances in the pathophysiology of the AD.

The investigators found this makeup was linked to an AD diagnosis, poor cognition, lower cerebrospinal fluid (CSF) levels of amyloid-β 1-42, increased amyloid-β deposition, higher CSF levels of phosphorylated tau and total tau, and reduced brain glucose metabolism.

Also, lower levels of ALT were tied to increased amyloid-β deposition, reduced brain glucose metabolism, greater brain atrophy, diagnosis of Alzheimer disease, and poor cognition.

“Consistent associations of serum-based liver function markers with cognitive performance and A/T/N biomarkers for AD highlight the involvement of metabolic disturbances in the pathophysiology of AD,” the authors wrote. “Further studies are needed to determine if these associations represent a causative or secondary role. Liver enzyme involvement in AD opens avenues for novel diagnostics and therapeutics.”

Of the 1581 participants in the study, 407 were cognitively normal older adults, 20 had significant memory concern, 298 had early mild cognitive impairment, 544 had late mild cognitive impairment, and 312 had AD. Data was collected between 2005 and 2013.

The investigators examined the associations of liver function markers with AD-associated clinical and amyloid, tau, and neurodegenerative biomarkers using generalized linear models adjusted for confounding variables and multiple comparisons.

They used 5 serum-based liver functions markers—total bilirubin; albumin; alkaline phosphatase; alanine aminotransferase; and aspartate aminotransferase—from the AD Neuroimaging Initiative as exposure variables.

The primary outcomes in the study included composite scores for AD diagnosis, executive functioning and memory, CSF biomarkers, atrophy measured by magnetic resonance imaging, brain glucose metabolism measured by fludeoxyglucose F 18 (¹⁸F) positron emission tomography, and amyloid-β accumulation measured by [¹⁸F] florbetapir positron emission tomography.

Peripheral blood levels of biochemical markers include albumin, alkaline phosphatase, ALT, AST, and total bilirubin are often used to assess liver function, as well as to measure liver injuries.

In 2012, investigators in Sweden began studying baseline spinal fluid samples from 137 people with mild memory impairment and monitored them for Alzheimer symptoms.

Their results showed that 91% of participants with low levels of beta-amyloid and high levels of tau (proteins that have previously been linked to Alzheimer) in the baseline samples went on to develop Alzheimer’s within the next 10 years, while those with normal levels of the biomarkers had no increased risk of developing the disease.

In addition, they showed that participants who developed Alzheimer’s within 5 years of the baseline sampling had significantly higher tau levels than those who developed it within 5 to 10 years.

The study, “Association of Altered Liver Enzymes with Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers,” was published online in Geriatrics.