Tau pathology closely tracks brain function during early AD

By Lucy Piper

Tau tangles may be a better indicator of cognitive changes during Alzheimer's disease (AD) progression than beta-amyloid (Aβ) deposition, researchers propose.

With the recently available positron emission tomography (PET) imaging of tau, Beau Ances (Washington University in St Louis, Missouri, USA) and colleagues were able to study topographies of tau deposition as well as those for Aβ in 10 patients with mild AD and make comparisons with 36 cognitively healthy adults.

They found that tau deposition was elevated in patients with AD and accurately discriminated affected patients from those without the condition based on the clinical dementia rating (CDR) scale, with the separation being more marked than that for Aβ topographies.

"Thus, as measured by the CDR, representation of tau topographies was more strongly associated with dementia status across participants," the team reports in Science Translational Medicine.

There was a very strong relationship between tau deposition and Aβ deposition but in different topographies, with tau deposition localised more in the temporal lobe and Aβ in frontal and parietal regions.

And tau deposition in the temporal regions, as well as globally, was also significantly associated with cerebrospinal fluid measures of tau often used to stage preclinical AD. The researchers note that this relationship was topographically specific and likely reflects the ordered nature of biomarker progression.

"[O]nce detectable tau pathology is present, there is already advanced Aβ pathology, allowing for a significant relationship", they suggest.

The team adds that "these lines of evidence suggest that the same pathological process is being measured by CSF and imaging techniques."

This finding gives weight to tau imaging being "an important marker of AD-related pathology", notes the team who found further evidence to support this when the participants completed neuropsychological tests across four domains of episodic, semantic, working memory and for visuospatial processing and an overall global measure.

For each cognitive domain, the weight attributed to PET tau in the best-fitting model was two- to ninefold greater than that attributed to PET Aβ, making PET tau the dominant topography in predicting cognitive function. Temporal lobe tau specifically was the strongest predictor of cognitive performance, which the researchers say suggests that "tauopathy severity in this region is sufficient to predict cognitive impairment across the early disease stages."

"These data suggest distinct roles of PET Aβ and tau imaging going forward. PET Aβ will likely remain a powerful tool for early detection of AD pathology during the preclinical period", they comment.

"However, our data suggest that the close relationship between PET tau and disease stage and symptomatology will be critical for tracking the efficacy of disease-modifying therapies."

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