Translocator protein (TSPO) genotype does not change cerebrospinal fluid levels of glial activation, axonal and synaptic damage markers in early Alzheimer's disease.

Background: PET imaging of the translocator protein (TSPO) is used to assess in vivo brain inflammation. One of the main methodological issues with this method is the allelic dependence of the radiotracer affinity. In Alzheimer's disease (AD), previous studies have shown similar clinical and patho-biological profiles between TSPO genetic subgroups.

Plasma neurofilament light chain in memory clinic practice: Evidence from a real-life study.

Objective: To explore the accuracy of plasma neurofilament light chain (NfL) as a biomarker for diagnosis and staging of cognitive impairment, in a large cohort with of previously diagnosed patients in clinical practice.

Methods: Retrospective, cross-sectional, monocentric study, from a tertiary memory clinic. Patients underwent cerebrospinal fluid core Alzheimer's disease (AD) biomarker evaluation using ELISA or Elecsys methods, and plasma NfL analysis using the single molecule array technology.

Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study.

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.

Exploring the link between GBA1 mutations and Dementia with Lewy bodies, A mini-review.

Importance: Dementia with Lewy bodies (DLB) is a neurodegenerative disease linked to abnormal accumulation of phosphorylated α-synuclein. GBA1 is the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), whose mutations are a risk factor of DLB.

Objective: To report all available data exploring the association between GBA1 mutations and DLB.

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study.

Background: Synaptic dysfunction is an early core feature of Alzheimer's disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology.

Efficacy and Safety of Ketone Supplementation or Ketogenic Diets for Alzheimer's Disease: A Mini Review.

Alzheimer's disease (AD) is the most frequent age-related neurodegenerative disorder, with no curative treatment available so far. Alongside the brain deposition of β-amyloid peptide and hyperphosphorylated tau, neuroinflammation triggered by the innate immune response in the central nervous system, plays a central role in the pathogenesis of AD. Glucose usually represents the main fuel for the brain.

Copper and zinc isotopic excursions in the human brain affected by Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is neuropathologically marked by amyloid beta (Aβ) plaques and neurofibrillary tangles. Little is known about isotopic compositions of human AD brains. Here we study this in comparison with control subjects for copper and zinc.

STAT3 inhibition protects against neuroinflammation and BACE1 upregulation induced by systemic inflammation.

Abnormal activation of the transcriptional factor STAT3 (signal transducer and activator of transcription 3) was recently associated with Alzheimer Disease (AD). STAT3 phosphorylation is critical for cytokine secretion linked to neuroinflammation. Moreover, STAT3 may act as a transcriptional regulator of BACE1 (β-APP cleaving enzyme-1), the key enzyme in amyloid β (Aβ) production.

CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer's disease.

Background: The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation.

Are ketogenic diets promising for Alzheimer's disease? A translational review.

Background: Brain amyloid deposition and neurofibrillary tangles in Alzheimer's disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production. Glucose metabolism is closely related to neuroinflammation. Ketogenic diets (KDs) include a high amount of fat, low carbohydrate and medium-chain triglyceride (MCT) intake.

What is the clinical impact of cerebrospinal fluid biomarkers on final diagnosis and management in patients with mild cognitive impairment in clinical practice? Results from a nation-wide prospective survey in France.

Objectives: New diagnostic criteria for Alzheimer's disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.

PKR knockout in the 5xFAD model of Alzheimer's disease reveals beneficial effects on spatial memory and brain lesions.

Brain lesions in Alzheimer's disease (AD) include amyloid plaques made of Aβ peptides and neurofibrillary tangles composed of hyperphosphorylated tau protein with synaptic and neuronal loss and neuroinflammation. Aβ oligomers can trigger tau phosphorylation and neuronal alterations through activation of neuronal kinases leading to progressive cognitive decline. PKR is a ubiquitous pro-apoptotic serine/threonine kinase, and levels of activated PKR are increased in AD brains and AD CSF.

LRRK2 impairs PINK1/Parkin-dependent mitophagy via its kinase activity: pathologic insights into Parkinson's disease.

Mutations of LRRK2, encoding leucine-rich repeat kinase 2 (LRRK2), are the leading cause of autosomal dominant Parkinson's disease (PD). The most frequent of these mutations, G2019S substitution, increases kinase activity, but it remains unclear how it causes PD. Recent studies suggest that LRRK2 modulates mitochondrial homeostasis.

Blood-Based Kinase Assessments in Alzheimer's Disease.

Alzheimer's disease (AD) is marked by memory disturbances followed by aphasia, apraxia and agnosia. Brain lesions include the accumulation of the amyloid peptide in extracellular plaques, neurofibrillary tangles with abnormally phosphorylated tau protein and synaptic and neuronal loss. New findings have suggested that brain lesions could occur one or two decades before the first clinical signs.

Phosphorylation of Parkin at serine 65 is essential for its activation .

Mutations in PINK1 and Parkin result in autosomal recessive Parkinson's disease (PD). Cell culture and studies have elaborated the PINK1-dependent regulation of Parkin and defined how this dyad orchestrates the elimination of damaged mitochondria via mitophagy. PINK1 phosphorylates ubiquitin at serine 65 (Ser65) and Parkin at an equivalent Ser65 residue located within its N-terminal ubiquitin-like domain, resulting in activation; however, the physiological significance of Parkin Ser65 phosphorylation in mammals remains unknown.

PKR modulates abnormal brain signaling in experimental obesity.

Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer's disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome ("metaflammasome") mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome.

Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop.

Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways.

Downregulated apoptosis and autophagy after anti-Aβ immunotherapy in Alzheimer's disease.

Aβ immunization of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunization, we have assessed the impact of previous Aβ immunization on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunized with AN1792 (iAD) and from 27 nonimmunized AD (cAD) cases was immunolabeled for proapoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3β ), p53 and Cdk5/p35.

PKR involvement in Alzheimer's disease.

Background: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation.

PINK1/Parkin-Dependent Mitochondrial Surveillance: From Pleiotropy to Parkinson's Disease.

Parkinson's disease (PD) is one of the most frequent neurodegenerative disease caused by the preferential, progressive degeneration of the dopaminergic (DA) neurons of the (SN) . PD is characterized by a multifaceted pathological process involving protein misfolding, mitochondrial dysfunction, neuroinflammation and metabolism deregulation. The molecular mechanisms governing the complex interplay between the different facets of this process are still unknown.