Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.

While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin.

Long COVID: Does SARS-CoV-2 induce lingering brain lesions?

Hundreds of millions of COVID cases have been reported so far and long-term lingering clinical symptoms are frequent and are called long COVID. Neurological signs including cognitive complaints are often described in long Covid. In COVID patients, the Sars-Cov-2 virus can reach the brain and could be responsible for cerebral anomalies observed in long COVID.

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.

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.

Cognitive decline and brainstem hypometabolism in long COVID: A case series.

Objective: To assess FDG cerebral PET in patients suffering from cognitive impairment linked to Long COVID. The COVID pandemic has affected dozens of millions of people around the world and has resulted in the deaths of more than 3 million people. Following the acute forms, it has been reported sometimes long forms of COVID, with involvements of several organs including the brain.

Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.

Introduction: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis.

Methods: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD).

Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex.

Many patients who have suffered from acute COVID infections have long-lasting symptoms affecting several organs including the brain. This long COVID status can include "brain fog" and cognitive deficits that can disturb activities of daily living and can delay complete recovery. Here, we report two cases of neurological long COVID with abnormal FDG PET findings marked by hypometabolic regions of the cingulate cortex.

The PKR/P38/RIPK1 Signaling Pathway as a Therapeutic Target in Alzheimer's Disease.

Neuropathological lesions in Alzheimer's disease (AD) include amyloid plaques formed by the accumulation of amyloid peptides, neurofibrillary tangles made of hyperphosphorylated tau protein, synaptic and neuronal degenerations, and neuroinflammation. The cause of AD is unknown, but according to the amyloid hypothesis, amyloid oligomers could lead to the activation of kinases such as eukaryotic translation initiation factor 2-alpha kinase 2 (PKR), p38, and receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which all belong to the same stress-activated pathway. Many toxic kinase activations have been described in AD patients and in experimental models.

Rationale, Design, and Methodology of a Prospective Cohort Study for Coping with Behavioral and Psychological Symptoms of Dementia: The RECage Project.

Background: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home.

Objective: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers.

Brain Glucose Metabolism in Cerebral Amyloid Angiopathy: An FDG-PET Study.

Background And Purpose: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their accuracy. Here we tested the hypothesis that FDG uptake is reduced in posterior cortical areas, particularly the primary occipital cortex, which pathologically bear the brunt of vascular Aβ deposition.

[ F]FDG PET may differentiate cerebral amyloid angiopathy from Alzheimer's disease.

Background: Cerebral amyloid angiopathy (CAA) is a frequent cause of both intracerebral hemorrhage (ICH) and cognitive impairment in the elderly. Diagnosis relies on the Boston criteria, which use magnetic resonance imaging markers including ≥2 exclusively lobar cerebral microbleeds (lCMBs). Although amyloid positron emission tomography (PET) may provide molecular diagnosis, its specificity relative to Alzheimer's disease (AD) is limited due to the prevalence of positive amyloid PET in cognitively normal elderly.

Full-length and C-terminal neurogranin in Alzheimer's disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays.

Background: Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer's disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease.

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.