Tau accumulation in brain likely best biomarker of short-term cognitive decline in Alzheimer’s

Reuters Health - 13/10/2021 -  For prediction of short-term cognitive decline in Alzheimer's disease (AD), tau accumulation in the brain on positron emission tomography (PET) is better than PET amyloid or cerebral spinal fluid (CSF) measurements of amyloid or tau, researchers say.

"Clinicians should be aware that when suspecting AD...tau PET scans should precede amyloid PET scans, which should be performed only if a tau PET is negative, since we show that all positive tau PET scans are also positive for amyloid," Dr. Marco Bucci of the Karolinska Institute told Reuters Health by email.

Principal investigator Dr. Agneta Nordberg, also of the Karolinska Institute, added by email, "When amyloid-beta starts to deposit in the brain, tau seem to be triggered by the spread of different concentrations to different parts of the brain," she explained. "Tau accumulation in brain as measured by PET seems to be a more sensitive biomarker in predicting cognitive symptoms than amyloid, fluorodeoxyglucose PET or CSF/plasma biomarkers."

Individuals can now be profiled based on their biomarker status for Abeta42 (A), tau (T) deposition and neurodegeneration (N), Drs. Bucci, Nordberg and colleagues report in Molecular Psychiatry. For this study, they compared cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category to assess their ability to predict longitudinal cognitive decline.

Two hundred and eight-two participants (mean age, about 72; about 45% men overall) in the Alzheimer's Disease Neuroimaging Initiative dataset were included, and grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Two hundred and thirteen of the participants were also monitored for three years with tests of episodic memory.

Various analyses showed moderate agreement between PET and CSF for A biomarkers, and only fair agreement for T biomarkers, as well as discordance for N biomarkers across all groups.

Baseline PET tau predicted longitudinal decline in episodic memory, regardless of CSF p-Tau181 positivity. Baseline PET tau and amyloid-beta also predicted decline in episodic memory; however, isolated PET amyloid-beta did not. Isolated PET tau positivity was observed in only two participants (0.71%).

While results for amyloid-beta were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not.

Further, PET tau positivity was superior to CSF p-Tau181 and PET amyloid-beta in predicting cognitive decline in AD during the three-year follow-up.

The authors state, "Our results provide support for the prioritization of PET tau over other biomarkers in the assessment of patients with cognitive impairment; if the result is then positive, there is a high chance of rapid cognitive decline."

Dr. Bucci added that the team will be studying second-generation tau PET tracers, which are more specific and less prone to off-target binding than first-generation tracers.

Dr. Hyun-Sik Yang, an associate neurologist at Brigham and Women's Hospital, noted in an email comment to Reuters Health that the study "was done in research participants in (North America) who agreed to PET scans, multiple study visits, and even to a lumbar puncture for CSF collection. Thus, participants may not fully represent the general population."

"Also," he noted, "although the study shows that tau PET may be more accurate than CSF tau in prognostication, these two tau markers were in good concordance (~75% in this study), and thus in most participants, choice of the test (CSF vs. PET) would not have made a difference."

"Finally, the sensitivity and specificity (and accuracy) of CSF and PET biomarkers depend on a specific threshold used, which varies across different labs," he said. "We clinicians should be cautious when interpreting an individual patient's CSF biomarker results, especially when the result is borderline abnormal, or when there is a discordance between CSF amyloid and tau measures."

ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and contributions from several pharmaceutical and biotech companies. The authors declare no competing interests.

SOURCE: https://go.nature.com/3FGQcnD Molecular Psychiatry, online October 1, 2021.

By Marilynn Larkin



Posted on 13 October 202120 October 2021