CSF Proenkephalin decreases with the progression of Huntington's disease

• Identifying molecular changes that contribute to the onset and progression of Huntington's disease (HD) is of importance for the development and evaluation of potential therapies. We conducted an unbiased mass-spectrometry proteomic analysis on the cerebrospinal fluid of 12 manifest HD patients (ManHD), 13 presymptomatic gene expansion carriers (pGEC) and 38 controls. In ManHD compared to pGEC 10 proteins were downregulated, and 43 upregulated. Decreased levels of proenkephalin (PENK) and transthyretin along with upregulated proteins (VASN, STC2, SGCE and C7) were all closely linked to HD symptom severity. The decreased PENK levels were replicated in a separate cohort of 23 ManHD and 23 controls where absolute quantitation was performed. We hypothesize that declining PENK levels reflect the degeneration of medium spiny neurons (MSNs) that produce PENK, and that assays for PENK may serve as a surrogate marker for the state of MSNs in HD.   

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Proteomics

Mass spectrometry

Neurodegeneration

Cerebrospinal fluid

Huntington's disease

Neurology

Neurologi

Publikations- och innehållstyp

vet (ämneskategori)

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