Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

Abstract

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.

Inflammasome-Inhibiting Nanoligomers are Neuroprotective Against Space-Induced Pathology in Healthy and Diseased 3D Human Motor and Pre-Frontal Cortex Brain Organoids

“…65 NGN that is a post-synaptic protein has been used as a clinical biomarker and observed to significantly increase with aging-related cognitive decline as well as in AD patients. 66,67 Similarly, NCAM-1 protein which has been associated with synaptic plasticity has now been shown to have a role in neuropathological conditions such as AD, MS, Schizophrenia, and others. 68 Besides cognition, many of these biomarkers have also been implicated and used in the detection of neuromuscular diseases like ALS, MS, and others.…”

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

“…The CSF Ng P75 and α-Syn levels were measured using commercially available ELISA kits, according to the manufacturer's instructions [30]. The CSF Aβ42, Aβ40, pTau and tTau levels, which represent AD-core biomarkers, were measured using the chemiluminescence enzyme immunoassay (CLEIA), using commercially available kits [4], according to the manufacturer's instructions.…”

“…The identification of specific biomarkers related to synaptic integrity, able to rapidly diagnose patients with AD and predict progression from mild cognitive impairment (MCI) to dementia, can be helpful in the prodromal and preclinical stages, which are potential targets for the early treatment of the disease. Among these, the role of neurogranin (Ng) and α-synuclein (α-Syn) in AD-related synaptic dysfunction/disruption was recently discussed [29][30][31][32].…”

Alzheimer's disease and COVID-19

“…Его уровни повышаются при некоторых нейродегенеративных заболеваниях, в том числе при БА. В частности, биохимический диагноз БА основывается на выявлении биомаркеров в ЦСЖ, характеризующейся снижением Aβ 42 и повышением уровней общего тау-протеина (t-Tau) и фосфорилированного тау-протеина (p-Tau) [86]. Некоторые авторы обнаружили, что у пациентов с COVID-19 наблюдается повышение уровня t-Tau в ЦСЖ, что свидетельствует о повреждении нейронов.…”

“…Рецепторы NMDA-типа в большом количестве находятся в клетках гиппокампа и коры [93]. Механизм обучения и памяти вызывает долговременную активацию нейронов, опосредованную нейротрансмиттером глутамата через NMDAрецепторы [86]. NMDA-рецепторы являются кальциевыми управляемыми каналами, которые участвуют во взаимодействиях вирус-хозяин.…”