Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.

Background: A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.

Methods: Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old.

Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial.

Background And Objectives: Improved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS.

Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Introduction: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).

Methods: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays and inter-platform Pearson correlations derived. Lumipulse Aβ42 measures were adjusted to incorporate standardization to certified reference materials.

Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.

Introduction: We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).

Methods: In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays, and inter-platform Pearson correlations were derived. Logistic regressions and receiver-operating characteristic analysis generated CSF cut-points optimizing concordance with F-florbetapir amyloid PET status (n = 63).

Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios.

Introduction: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration.

Methods: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ, Aβ, and Aβ peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay.

CSF neurogranin or tau distinguish typical and atypical Alzheimer disease.

Objective: To assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease.

Methods: Immunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls ( = 27), biomarker-proven amnestic Alzheimer's disease ( = 68), and the atypical visual variant of Alzheimer's ( = 19) according to international criteria. CSF total-tau, Aβ42, and neurofilament light concentrations were investigated using commercially available assays.

Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation.

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development.

Increased CSF neurogranin concentration is specific to Alzheimer disease.

Objective: To assess the specificity of the dendritic protein neurogranin (Ng) in CSF from patients with a broad range of neurodegenerative diseases including a variety of dementias, tauopathies, and synucleinopathies.

Method: An optimized immunoassay was used to analyze CSF Ng in a retrospective cohort of 331 participants with different neurodegenerative diseases, including healthy controls (n = 19), biomarker-proven Alzheimer disease (AD) (n = 100), genetic AD (n = 2), behavioral variant frontotemporal dementia (n = 20), speech variant frontotemporal dementia (n = 21), Lewy body dementia (n = 13), Parkinson disease (n = 31), progressive supranuclear palsy (n = 46), multiple system atrophy (n = 29), as well as a heterogeneous group with non-neurodegenerative cognitive impairment (n = 50). CSF Ng concentrations and correlations of CSF Ng with total tau, phosphorylated tau, and β-amyloid 42 concentrations, Mini-Mental State Examination score, and disease duration in the different groups were investigated.