James Scott Miners
Affiliation: University of Bristol
Miners J, van Helmond Z, Chalmers K, Wilcock G, Love S, Kehoe P. Decreased expression and activity of neprilysin in Alzheimer disease are associated with cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2006;65:1012-21 pubmed
..However, logistic regression analysis showed low NEP levels to be a significant independent predictor of moderate to severe CAA. ..
Miners J, Kehoe P, Love S. Immunocapture-based fluorometric assay for the measurement of insulin-degrading enzyme activity in brain tissue homogenates. J Neurosci Methods. 2008;169:177-81 pubmed publisher
..This assay should allow the measurement of IDE enzyme levels in a variety of biological tissues and may be useful in study of diseases such as Alzheimer's disease and insulin-dependent diabetes. ..
Miners J, Ashby E, Van Helmond Z, Chalmers K, Palmer L, Love S, et al
. Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer's disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2008;34:181-93 pubmed
..Increased ACE-1, probably of neuronal origin, accumulates perivascularly in severe CAA and colocalizes with vascular ECM. The possible relationship of ACE-1 to the deposition of perivascular ECM remains to be determined. ..
Miners J, Verbeek M, Rikkert M, Kehoe P, Love S. Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid. J Neurosci Methods. 2008;167:229-36 pubmed
..The assay allows high-throughput analysis and, critically, also ensures a high level of enzyme specificity even when assaying crude tissue homogenates or CSF. ..
Miners J, Kehoe P, Love S. Neprilysin protects against cerebral amyloid angiopathy and A?-induced degeneration of cerebrovascular smooth muscle cells. Brain Pathol. 2011;21:594-605 pubmed publisher
..Our findings suggest that NEP protects CVSMCs from A? toxicity and protects cerebral blood vessels from the development and complications of CAA. ..
Miners J, Barua N, Kehoe P, Gill S, Love S. A?-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol. 2011;70:944-59 pubmed publisher
..In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other A?-degrading enzymes may offer advantages. ..
Swirski M, Miners J, de Silva R, Lashley T, Ling H, Holton J, et al
. Evaluating the relationship between amyloid-? and ?-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson's disease. Alzheimers Res Ther. 2014;6:77 pubmed publisher
..Together, these data show that the concentration of pSer129 ?-syn in brain tissue homogenates is directly related to the level of A? and Braak tangle stage, and predicts cognitive status in Lewy body diseases. ..
Miners J, Baig S, Tayler H, Kehoe P, Love S. Neprilysin and insulin-degrading enzyme levels are increased in Alzheimer disease in relation to disease severity. J Neuropathol Exp Neurol. 2009;68:902-14 pubmed publisher
..Our findings suggest that reduction in NEP and IDE activity is not the primary cause of beta-amyloid accumulation in AD, but rather a late-stage phenomenon secondary to neurodegeneration. ..
Miners J, Morris S, Love S, Kehoe P. Accumulation of insoluble amyloid-? in down's syndrome is associated with increased BACE-1 and neprilysin activities. J Alzheimers Dis. 2011;23:101-8 pubmed publisher
..These findings provide strong support that BACE-1 and NEP activities, but not ACE, increase in response to the accumulation of insoluble A? within the brain. ..