Association between plasma exosome neurogranin and brain structure in patients with Alzheimer’s disease: a protocol study

Abstract

IntroductionNeurogranin is known to be significantly elevated in patients with Alzheimer’s disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD.Methods and analysisIn this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples.Ethics and disseminationThe ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences.Trial registration numberChiCTR2000029055.

Association of region‐specific hippocampal reduction of neurogranin with inflammasome proteins in post mortem brains of Alzheimer's disease

“…Using a test of circularity, we found that the neurons with Ng expression in the CA2 and CA3 regions of AD cases had increased circularity compared to the controls. This finding indicates that the loss of synaptic structure underlies the impaired synaptic function and loss of plasticity, which accounts for the cognitive impairment associated with intermediate AD pathology via the loss of neuronal structure 34 …”

“…This finding indicates that the loss of synaptic structure underlies the impaired synaptic function and loss of plasticity, which accounts for the cognitive impairment associated with intermediate AD pathology via the loss of neuronal structure. 34 Tau is expressed in six isoforms and has two N-terminal domains and four microtubule-binding repeat domains composed of ( 3 R or 4 R). In AD pathology, tau phosphorylates and forms insoluble paired helical filaments that contain both 3 R and 4 R tau.…”

“…This finding indicates that the loss of synaptic structure underlies the impaired synaptic function and loss of plasticity, which accounts for the cognitive impairment associated with intermediate AD pathology via the loss of neuronal structure. 34 …”

Modulation of Amyloid-β and Tau in Alzheimer’s Disease Plasma Neuronal-Derived Extracellular Vesicles by Cerebrolysin® and Donepezil

“…Another study found that a mindfulness-based stress reduction intervention increased plasma REST levels compared with a placebo intervention in older adults with psychiatric risk factors for AD, and that elevated REST levels were associated with a reduction in psychiatric symptoms related to stress and AD risk [ 26 ]. The protocol of a clinical trial aimed at investigating the associations of plasma NDEV NRGN with changes in brain structures and cognition in early AD stages has also been published recently [ 62 ].…”

Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives

“…However, plasma biomarkers for synaptic dysfunction often do not reflect damage to the brain, and a possible reason is their production in peripheral tissues [ 99 ]. Although the performance of the direct testing of synaptic biomarkers in plasma is unsatisfactory, the plasma NDEs of these biomarkers perform well, and they are worthy of further exploration for clinical application as one part of X in the peripheral A-T-N-X framework [ 37 , 99 , 100 ].…”