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MATRIX METALLOPROTEINASE 10 IS LINKED TO THE RISK OF PROGRESSION TO DEMENTIA OF THE ALZHEIMER’S TYPE
Abstract
Aims
To identify cerebrospinal fluid (CSF) proteins associated with Alzheimer’s disease progression along with the clinical disease staging.
Methods
We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n=410; German DCN, n=93; German Mannheim, n=53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer’s type (DAT).
Results
Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 showed a higher probability of progressing to DAT and a faster cognitive decline. CSF matrix metalloproteinase 10 increased the prediction accuracy of CSF Aβ42, P-tau181, and T-tau for conversion to DAT. Including matrix metalloproteinase 10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181, and T-tau. Matrix metalloproteinase 10 was correlated with age in subjects with normal Aβ42, P-tau181, and T-tau levels.
Conclusions
Our findings support the use of CSF matrix metalloproteinase 10 as a prognostic marker for DAT and its inclusion to the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of matrix metalloproteinase 10 may reflect ageing and neuroinflammation.