AT ANA 2017

SAN DIEGO (FRONTLINE MEDICAL NEWS) – In patients with Lewy body disease, cerebrospinal fluid biomarkers may predict the extent of Alzheimer’s disease pathology, according to a new postmortem analysis.

In the small prospective study, David Irwin, MD, and his colleagues at the University of Pennsylvania, Philadelphia, found that higher antemortem cerebrospinal fluid (CSF) levels of total tau (t-tau) protein and lower amyloid-beta 1-42 (Abeta 1-42) levels were associated with postmortem evidence of cerebral Alzheimer’s disease and synuclein pathology.

The connection between CSF Abeta 1-42 and tau protein has been shown in Alzheimer’s disease, but not Lewy body disease (LBD).

The findings could have prognostic indications because about 40% of LBD patients have enough Abeta 1-42 and tau tangle pathology to have a secondary diagnosis of Alzheimer’s disease, and greater Alzheimer’s disease pathology has been linked to shorter survival. It could also help individualize therapy, as LBD patients with more Alzheimer’s disease character could be expected to respond better to antisynuclein and Alzheimer’s therapies, according to Dr. Irwin, who presented the study at a poster session at the annual meeting of the American Neurological Association.

In fact, the CSF ratio of CSF t-tau/Abeta 1-42 predicted the presence or absence of Alzheimer’s disease pathology with 90% sensitivity and 100% specificity.

If the results from the small study hold up, “we can identify who has Alzheimer’s copathology and who has a more aggressive form of Lewy body disease where it’s reaching the cortex rather than being in the brain stem, and that correlates with memory loss, dementia, and other things that impair the patient’s functioning,” Dr. Irwin said in an interview.

The study was possible because the Udall Center for Parkinson’s Research at the University of Pennsylvania has an active autopsy program and a significant number of Parkinson’s disease patients who have donated their brain for research. “It’s very rare to have autopsy-confirmed samples where we can validate what we’re measuring in the spinal fluid to what is actually accumulating in the brain,” Dr. Irwin said.

The study included 24 patients with autopsy-confirmed LBD who had undergone CSF testing while they were still alive. The researchers calculated ordinal pathology scores of tau tangles, Abeta 1-42 plaques, and alpha-synuclein pathology across seven regions of the brain, producing a global pathology score for each variable. The subjects were then divided into two groups: Lewy body synuclein stages with medium to high Alzheimer’s copathology (SYN+AD, n = 10) and those with low to no Alzheimer’s copathology (SYN-AD, n = 14).

In the CSF, the researchers analyzed associations with t-tau, phosphorylated tau (p-tau), and Abeta 1-42. They found that Abeta 1-42 levels were significantly different between SYN+AD and SYN-AD patients (147.2 pg/mL vs. 231.1 pg/mL, respectively; P = .001), as were CSF t-tau levels (63.9 pg/mL vs. 36.9 pg/mL; P = .02). P-tau was not significantly different (20.2 pg/mL vs. 15.5 pg/mL; P = 0.3), which was a surprise since it “is usually the strongest correlate of tangles in the brain,” Dr. Irwin said.

A ratio of CSF t-tau/Abeta 1-42 higher than 0.30 distinguished between SYN+AD and SYN-AD (area under the curve, 0.92; 95% confidence interval, 0.7-1.0; 90% sensitivity, 100% specificity), while CSF Abeta 1-42 less than 185 pg/mL distinguished neocortical synuclein stage (AUC, 0.92; 95% CI, 0.54-0.94; 77% sensitivity, 82% specificity).

The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Irwin reported having no financial disclosures.

cnnews@frontlinemedcom.com

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