Disease Area Neurological, Diagnostics & prognostics

Alzheimer’s Awakening

The ongoing fight against Alzheimer’s disease (AD) is tough, with few victories along the way. Much of the problem is a battle of recognition; by the time AD is symptomatic, the majority of amyloid-beta (Aβ) accumulation has already occurred, and tau pathology is often already well established. In short, the damage may have already been done. To access the therapeutic window before cognitive symptoms occur, clinicians have been seeking indicators of early AD wherever they can find them; for example, preliminary studies in mice have suggested that decreased non-rapid eye movement (NREM) sleep slow wave activity may be associated with Aβ accumulation.

Brendan Lucey – Assistant Professor of Neurology at the Washington University School of Medicine in St Louis, Missouri, says, “We think that slow wave activity – which is thought to be important for memory consolidation – will be an important marker for early AD pathology.” To that end, Lucey is first author on a study that employed single-channel electroencephalography (EEG) to monitor the sleep activity of AD patients alongside a range of AD specific tests, including cognitive performance, brain imaging, and cerebrospinal fluid (CSF) analysis. The results echoed other studies: NREM SWA was inversely related to AD pathology, particularly tauopathy (1).

Lucey and the team hypothesize that tau accumulation disrupts normal slow wave activity just before or soon after problems with cognition and memory start. But when exactly do these NREM sleep changes occur in relation to progression of amyloid and tau pathology? “We need longitudinal studies to determine this timing,” says Lucey, recognizing the criticality of this missing information.

But that doesn’t mean the knowledge gained so far holds no clinical value. “Measuring NREM slow wave activity or other changes in sleep-wake activity (along with other factors) may be a way to non-invasively and inexpensively screen for risk for cognitive decline due to AD,” says Lucey. “This would be very helpful in future clinical trials and possibly screening in the clinic.”

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  1. B P Lucey et al. “Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease.” Sci Transl Med. 11, 474. (2019) PMID: 30626715.
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Jonathan James

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