In the Journals

Liver functioning may play role in Alzheimer’s pathophysiology

Altered liver function markers appeared associated with Alzheimer’s disease diagnosis and impaired memory and executive function, as well as amyloid-, tau and neurodegenerative biomarkers of Alzheimer’s pathophysiology, according to study results published in JAMA Network Open.

“Mounting evidence suggests that patients with Alzheimer disease (AD) display metabolic dysfunction. Focused investigation to assess the role of liver function in AD and its endophenotypes is required to bridge the gap between these observations,” Kwangsik Nho, PhD, of the Indiana Alzheimer Disease Center at Indiana University School of Medicine, and colleagues wrote.

Researchers measured serum-based liver function markers, cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism and amyloid- accumulation among 1,581 participants in the AD Neuroimaging Initiative to assess whether liver function markers were tied to cognitive dysfunction and amyloid, tau and neurodegeneration (A/T/N) biomarkers.

Exposure variables included five serum-based liver function markers — total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase.

Of the 1,581 participants (697 women; mean age 73.4 years), 407 were cognitively normal, 20 had significant memory concern, 298 had early mild cognitive impairment, 544 had late mild cognitive impairment and 312 had Alzheimer’s disease.

Nho and colleagues found that increased aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and decreased levels of ALT were linked to Alzheimer’s diagnosis (AST to ALT ratio: OR = 7.932; 95% CI, 1.673-37.617, and ALT: OR = 0.133; 95% CI, 0.042-0.422) and poor cognitive performance (including both memory and executive function).

The investigators reported that elevated AST to ALT ratio values were also tied to reduced CSF levels of amyloid- 1-42 and brain glucose metabolism as well as increased amyloid- deposition and CSF levels of phosphorylated tau and total tau. In addition, lower ALT levels were tied to increased amyloid- deposition, decreased brain glucose metabolism and greater brain atrophy.

“These results are, to our knowledge, the first to show an association of peripheral markers of liver functioning with central biomarkers associated with AD,” Nho and colleagues wrote. “Although our results suggest an important role of liver functioning in AD pathophysiological characteristics, the causal pathways remain unknown. The liver-brain biochemical axis of communication should be further evaluated in model systems and longitudinal studies to gain deeper knowledge of causal pathways.” – by Savannah Demko

Disclosure: Nho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Altered liver function markers appeared associated with Alzheimer’s disease diagnosis and impaired memory and executive function, as well as amyloid-, tau and neurodegenerative biomarkers of Alzheimer’s pathophysiology, according to study results published in JAMA Network Open.

“Mounting evidence suggests that patients with Alzheimer disease (AD) display metabolic dysfunction. Focused investigation to assess the role of liver function in AD and its endophenotypes is required to bridge the gap between these observations,” Kwangsik Nho, PhD, of the Indiana Alzheimer Disease Center at Indiana University School of Medicine, and colleagues wrote.

Researchers measured serum-based liver function markers, cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism and amyloid- accumulation among 1,581 participants in the AD Neuroimaging Initiative to assess whether liver function markers were tied to cognitive dysfunction and amyloid, tau and neurodegeneration (A/T/N) biomarkers.

Exposure variables included five serum-based liver function markers — total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase.

Of the 1,581 participants (697 women; mean age 73.4 years), 407 were cognitively normal, 20 had significant memory concern, 298 had early mild cognitive impairment, 544 had late mild cognitive impairment and 312 had Alzheimer’s disease.

Nho and colleagues found that increased aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and decreased levels of ALT were linked to Alzheimer’s diagnosis (AST to ALT ratio: OR = 7.932; 95% CI, 1.673-37.617, and ALT: OR = 0.133; 95% CI, 0.042-0.422) and poor cognitive performance (including both memory and executive function).

The investigators reported that elevated AST to ALT ratio values were also tied to reduced CSF levels of amyloid- 1-42 and brain glucose metabolism as well as increased amyloid- deposition and CSF levels of phosphorylated tau and total tau. In addition, lower ALT levels were tied to increased amyloid- deposition, decreased brain glucose metabolism and greater brain atrophy.

“These results are, to our knowledge, the first to show an association of peripheral markers of liver functioning with central biomarkers associated with AD,” Nho and colleagues wrote. “Although our results suggest an important role of liver functioning in AD pathophysiological characteristics, the causal pathways remain unknown. The liver-brain biochemical axis of communication should be further evaluated in model systems and longitudinal studies to gain deeper knowledge of causal pathways.” – by Savannah Demko

Disclosure: Nho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.