Dipeptidyl peptidase-4 (DPP4) has been proven to exert its functions by both enzymatic and nonenzymatic pathways. The nonenzymatic function of DPP4 in diabetes-associated cognitive impairment remains unexplored. We determined DPP4 protein concentrations or its enzymatic activity in type 2 diabetic patients and db/db mice and tested the impact of the non-enzymatic function of DPP4 on mitochondrial dysfunction and cognitive impairment both in vivo and in vitro. The results show that increased DPP4 activity was an independent risk factor for incident mild cognitive impairment (MCI) in type 2 diabetic patients. In addition, DPP4 was highly expressed in the hippocampus of db/db mice and contributed to mitochondria dysfunction and cognitive impairment. Mechanistically, DPP4 might bind to PAR2 in the hippocampus and trigger GSK-3β activation, which downregulates peroxisome proliferator-activated receptor gamma coactivator 1 alpha expression and leads to mitochondria dysfunction, thereby promoting cognitive impairment in diabetes. Our findings indicate that the nonenzymatic function of DPP4 might promote mitochondrial dysfunction and cognitive impairment in diabetes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/alz.12437 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma phosphorylated tau and neuropsychiatric symptoms in dementia with Lewy bodies.
Alzheimers Dement
December 2024
Centre for Healthy Brain Ageing, Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
Introduction: Neuropsychiatric symptoms (NPSs) are common in dementia with Lewy bodies (DLB) but their neurobiological mechanisms are poorly understood.
Methods: NPSs and cognition were assessed annually in participants (DLB n = 222; Alzheimer's disease [AD] n = 125) from the European DLB (E-DLB) Consortium, and plasma phosphorylated tau-181 (p-tau181) and p-tau231 concentrations were measured at baseline.
Results: Hallucinations, delusions, and depression were more common in DLB than in AD and, in a subgroup with longitudinal follow-up, persistent hallucinations and NPSs were associated with lower p-tau181 and p-tau231 in DLB.
The role of neuropsychological assessment in the evaluation of patients with cognitive-behavioral change due to suspected Alzheimer's disease and other causes of cognitive impairment and dementia.
Alzheimers Dement
December 2024
Northwestern Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Chicago, Illinois, USA.
The Alzheimer's Association convened a Diagnostic Evaluation, Testing, Counseling and Disclosure Clinical Practice Guideline workgroup to help combat the major global health challenges surrounding the timely detection, accurate diagnosis, and appropriate disclosure of mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) or other diseases that cause these types of cognitive-behavioral disorders. The newly published clinical practice guidelines are proposed as a structured approach to evaluation. The purpose of the present article is to provide a clinical perspective on the use of neuropsychology within the new framework and practice guidelines outlined under the Diagnostic Evaluation, Testing, Counseling and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD) recommendations for primary care and specialty care.
View Article and Find Full Text PDFLongitudinal synaptic loss versus tau Braak staging in amnestic mild cognitive impairment.
Alzheimers Dement
December 2024
Nuclear Medicine and Molecular Imaging, Imaging and Pathology, KU Leuven, Leuven, Belgium.
Introduction: The longitudinal progression of synaptic loss in Alzheimer's disease (AD) and how it is affected by tau pathology remains poorly understood.
Methods: Thirty patients with amnestic mild cognitive impairment (aMCI) and 26 healthy controls underwent cognitive evaluations and tau, synaptic vesicle protein 2A (SV2A), and amyloid positron emission tomography. Twenty-one aMCI underwent 2-year follow-up (FU) investigations.
Introduction to the DETeCD-ADRD special issue.
Alzheimers Dement
December 2024
Banner Sun Health Research Institute and Banner Alzheimer's Institute, Banner Health, Sun City, Arizona, USA.
This special issue contains multiple articles related to the DETeCD-ADRD guideline.
View Article and Find Full Text PDFAre abnormalities in lipid metabolism, together with adverse childhood experiences, the silent causes of immune-linked neurotoxicity in major depression?
Neuro Endocrinol Lett
December 2024
Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Background: Severe or recurring major depression is associated with increased adverse childhood experiences (ACEs), heightened atherogenicity, and immune-linked neurotoxicity (INT). Nevertheless, the interconnections among these variables in outpatient major depression (OMDD) have yet to be determined. We aim to determine the correlations among INT, atherogenicity, and ACEs in OMDD patients compared to normal controls.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!