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Comment
. 2023 Nov 22;43(47):7899-7901.
doi: 10.1523/JNEUROSCI.1440-23.2023.

Unraveling the Mechanisms Underlying Disordered Sleep in Alzheimer's Disease

Russell Luke  1 , Irina Alymova  1   2
Affiliations
Comment

Unraveling the Mechanisms Underlying Disordered Sleep in Alzheimer's Disease

Russell Luke et al. J Neurosci. .
No abstract available

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Figures

Figure 1.
Figure 1.
Proposed brain circuits involved in sleep disturbances of PS19 mice. A, In young PS19 mice, tau pathology predominantly affects wake-promoting structures including, but not limited to, the LC, lateral hypothalamus (LH), and tuberomammillary nucleus (TMN). This early tau pathology may lead to abnormal firing of wake-promoting cells during sleep, consequently inhibiting the thalamic reticular nucleus (TRN), thalamic relay cells, and cortical regions involved in spindle control. With age, tau pathology expands to more regions, including to thalamocortical circuits, NREM-promoting neurons of the ventrolateral preoptic area (VLPO) and parafacial zone (PZ), as well as REM-promoting SLD neurons. Correspondingly, pathology in these regions would result in exacerbation of spindle deficits, decreased and fragmented sleep, and RBD symptoms as seen in old PS19 mice. B, We propose that DORA-12 treatment reduces sleep disturbances in old PS19 mice by antagonizing orexin signaling onto wake-promoting circuits. This would facilitate the invigoration of surviving spindle- and sleep-generating neurons, thus increasing sleep amount, as well as, respectively, restoring spindles and muscle suppression during NREM and REM.
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