Cerebrospinal fluid neurogranin/β‐site APP‐cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 4 - Trang 617-627 - 2018
Bjørn-Eivind Kirsebom1,2, Kaja Nordengen3,4, Per Selnes3,4, Knut Waterloo1,2, Silje Bøen Torsetnes3, Berglind Gísladóttir3,5, Britta Brix6, Eugeen Vanmechelen7, Geir Bråthen8,9, Erik Hessen3,10, Dag Aarsland11,12, Tormod Fladby3,4
1Department of Neurology, University Hospital of North Norway, Tromsø, Norway
2Department of Psychology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
3Department of Neurology, Akershus University Hospital, Lørenskog, Norway
4Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway
5Molecular Biology (EpiGen), Institute of Clinical Medicine, University of Oslo, Akershus University Hospital, Lørenskog, Norway
6Euroimmun, Lübeck, Germany
7ADx NeuroSciences NV, Gent, Belgium
8Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
9Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim, Trondheim, Norway
10Department of Psychology, University of Oslo, Oslo, Norway
11Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway
12Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK

Tóm tắt

AbstractIntroductionThe cerebrospinal fluid neurogranin (Ng)/β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta‐amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer's disease.MethodsWe compared Ng/BACE1 levels between cases with subjective cognitive decline (n = 18) and mild cognitive impairment (n = 20) both with amyloid plaques and healthy controls (APOE‐ε4+, n = 16; APOE‐ε4‐, n = 20). We performed regression analyses between cerebrospinal fluid levels, baseline hippocampal and amygdala volumes, and pertinent cognitive measures (memory, attention, Mini Mental State Examination [MMSE]) at baseline and after 2 years.ResultsNg/BACE1 levels were elevated in both subjective cognitive decline and mild cognitive impairment compared to healthy controls. Higher Ng/BACE1 ratio was associated with lower hippocampal and amygdala volumes; lower baseline memory functions, attention, and MMSE; and significant decline in MMSE and memory function at 2‐year follow‐up.DiscussionHigh Ng/BACE1 ratio predicts cognitive decline also in preclinical cases with amyloid plaques.

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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 4

617-627

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