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Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

Identifieur interne : 000008 ( Main/Exploration ); précédent : 000007; suivant : 000009

Dysfunction of the locus coeruleus–norepinephrine system and related circuitry in Parkinson's disease-related dementia

Auteurs : Kelly Del Tredici [Allemagne] ; Heiko Braak [Allemagne]

Source :

RBID : ISTEX:AEE88DD3F1B814401B913BA56F7EFE2D1CFFB21A

Abstract

Although resting tremor, cogwheel rigidity, hypokinesia/bradykinesia and postural instability usually dominate the clinical picture of sporadic Parkinson's disease (PD), both clinical and epidemiological data reveal that a wide variety of additional symptoms impair patients’ quality of life considerably, parallel to the chronic progressive neurodegenerative movement disorder. Autopsy based retrospective studies have shown that α-synuclein immunoreactive Lewy pathology (LP) develops in the locus coeruleus (LC) of patients with neuropathologically confirmed sporadic PD, as well as in individuals with incidental (prodromal or premotor) Lewy body disease but not in age and gender matched controls. Using five case studies, this review discusses the possible role of LP (axonopathy, cellular dysfunction and nerve cell loss) in the LC, catecholaminergic tract and related circuitry in the development of PD-related dementia. The contribution of noradrenergic deficit to cognitive dysfunction in PD has been underappreciated. Noradrenergic therapeutic interventions might not only alleviate depressive symptoms and anxiety but also delay the onset of cognitive decline.

Url:
DOI: 10.1136/jnnp-2011-301817


Affiliations:


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