Changes in Alzheimer’s Biomarkers May Provide Clues About Parkinson’s Progression

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Subtle changes in the levels of Alzheimer’s disease biomarkers in patients at the earlier stages of Parkinson’s disease may provide clues about the evolution of their motor and cognitive functions, a study says.

The study, “Evolution of Alzheimer’s Disease Cerebrospinal Fluid Biomarkers in Early Parkinson’s Disease,” was published in the Annals of Neurology.

Although Parkinson’s is mainly characterized by the buildup of aggregates of the protein alpha-synuclein (Lewy bodies) in the brain, accumulation of other toxic proteins also have been observed in some patients. These include beta-amyloid plaques and tau tangles made up of aggregates of beta-amyloid or tau protein, which are both hallmarks of Alzheimer’s.

“[A]pproximately 30% of autopsy-confirmed PD [Parkinson’s disease] have sufficient postmortem plaque and tangle pathology [disease] to meet … criteria for a second diagnosis of AD [Alzheimer’s disease], and these patients have a more rapid decline in cognition and overall survival than PD patients with minimal AD co-pathology,” researchers wrote.

These observations raised the possibility that classic biomarkers of Alzheimer’s could be used to estimate the clinical decline observed in patients with Parkinson’s.

To explore that possibility, researchers at the University of Pennsylvania  measured the levels of three biomarkers of Alzheimer’s — amoyloid-beta (Abeta42), total tau (t-tau), and phosphorylated tau (p-tau) — in cerebrospinal fluid (CSF) samples collected from 416 patients with early Parkinson’s over the course of three years.

(Of note, CSF is the fluid that surrounds the brain and spinal cord; phosphorylation is a chemical modification in which a phosphate group is added to a protein.)

In parallel, they also measured the levels of the same biomarkers in CSF samples taken from 192 healthy individuals, who were used as controls. Both patients and healthy individuals participated in the Parkinson’s Progression Markers Initiative (PPMI), an observational clinical study and the largest dataset ever compiled for Parkinson’s disease research.

Analyses showed that at the start of the study, the median levels of t-tau (157.7 versus 173.5 picograms per mililiter (pg/mL)), p‐tau (13.4 versus 15.4 pg/mL), and Abeta42 (846.2 versus 926.5 pg/mL) were all lower in patients with early Parkinson’s compared to controls.

The percentage of individuals with low levels of Abeta42 indicative of disease (pathologically-low levels) at the start of the study was slightly higher among those with Parkinson’s (31.5%), compared to controls (27.7%).

Additional analyses found that Abeta42 levels measured at the study’s start could be used to predict small, but measurable, changes on patients’ cognitive, motor, and autonomic functions (body responses regulated by the nervous system without a conscious effort).

When investigators analyzed changes in the levels of these biomarkers over the course of three years, they found that patients with early Parkinson’s had a stronger reduction in the levels of Abeta42 and p‐tau compared to healthy individuals.

Levels of t-tau and p-tau remained relatively stable in patients until the second or third year of follow-up, when a mild increase was observed. Conversely, in healthy individuals, the levels of both biomarkers tended to rise overtime.

“Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, while modest over a three-year period, suggest biomarker profiles in PD may deviate from healthy aging,” the researchers wrote.
“Further follow-up of the PPMI cohort and other ongoing longitudinal PD studies will be needed to determine predictive value for clinically relevant changes,” they concluded.

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