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Research highlights potential Alzheimer’s disease biomarker, finds biomarkers unaffected by cognitive, physical activity

Autolysosomnal proteins may be a significant Alzheimer’s disease biomarker, as study findings in Neurology show patients with the disease exhibited higher levels of the proteins than healthy controls.

“There is an urgent need for biomarkers that accurately detect pathogenic components of Alzheimer’s disease before appearance of neurologic signs. Early treatments directed to such targets could limit or reverse neuronal damage and prevent development of overt [Alzheimer’s disease],” study researcher Edward J. Goetzl, MD, of the University of California, San Francisco, and colleagues wrote. “Recent analyses of neurally derived plasma exosomal proteins have shown significantly higher levels of the pathogenic proteins P-T181-tau, P-S396-tau, and beta-amyloid 1-42 in [Alzheimer’s disease] than in case controls.”

Researchers compared blood exosomes obtained from patients with Alzheimer’s disease (n=46) or frontotemporal dementia (n=16) when cognitively normal and 1 to 10 years later when diagnosed with case controls.

Analysis indicated patients with Alzheimer’s disease had higher mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 and ubiquitinylated proteins compared with controls (P ≤ .0005). These levels were also higher among patients with Alzheimer’s disease vs. those with dementia (P ≤ .006).

Mean exosomal levels of heat-shock protein 70 were lower among patients with Alzheimer’s disease vs. controls (P ≤ .0005).

All patients with Alzheimer’s disease were correctly identified by step-wise discriminant modeling of protein levels.

“Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of [Alzheimer’s disease] (P ≤ .0003),” according to researchers. “These preliminary results confirm in living patients with [Alzheimer’s disease] the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies.”

Effect of cognitive, physical activity on Alzheimer’s disease

Results from a second study published in Neurology indicate that past or current cognitive activity and recent physical activity did not have a protective effect on Alzheimer’s disease biomarkers.

To examine potential relationships between lifestyle factors and Alzheimer’s disease biomarkers, study researcher Christopher M. Gidicsin, BA, of Massachusetts General Hospital and Harvard Medical School, and colleagues assessed past and current cognitive and physical activity among 186 clinically normal adults with a mean age of 74 years.

Linear regression analyses indicated past and current cognitive activity were associated with one another (P < .0001), with higher education (P < .0001) and higher scores on the American version of the National Adult Reading Test (P < .0001).

Pittsburgh compound B-PET retention, greater ¹⁸F-fluorodeoxyglucose uptake and hippocampal volume were not significantly associated with cognitive or physical activity.

“These results add to the current literature and align well with the results of other studies with large sample sizes, finding a relationship between lifelong cognitive activity and current neuropsychological testing performance without a direct relationship between cognitive or physical activity and biomarkers of [Alzheimer’s disease],” Gidicsin and colleagues wrote. – by Amanda Oldt

Disclosure: Goetzl reports financial ties with Nanosomix. Please see the full study for a list of all other authors’ relevant financial disclosures. Gidicsin and colleagues report no relevant financial disclosures.