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Brainstem serotonin and norepinephrine producing nuclei (dorsal raphe nucleus and locus coeruleus, respectively) are vulnerable to cell loss, tau deposition and -synuclein pathology early in normal aging, AD and PD [59, 60, 61] This early involvement of brainstem nuclei is thought to contribute to the high prevalence of depression, anxiety, and sleep disturbance, preceding cognitive decline and motor symptom onset [61,62,63,64,65]

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