Current status of fluid biomarkers for early Alzheimer's disease and FDA regulation implications.

Many changes can now be seen in the development and use of tests, especially those incorporating fluid biomarkers, to diagnose Alzheimer's disease (AD), a devastating disease caused by the progressive but rapid degeneration of cortical tissue. Some biomarkers we already know have a significant association with AD, such as amyloid beta (Aβ) and tau, as well as the ratio of concentrations of other Aβ isoforms. In addition, several novel biomarkers are emerging that can also be used as diagnostic fluid biomarkers for AD, but many studies are still needed before we can consider them reliable.

Increased oligomeric TDP-43 in the plasma of Korean frontotemporal dementia patients with semantic dementia.

Introduction: Semantic dementia (SD) is a progressive neurodegenerative disease associated with impaired vocabulary that progresses to memory impairment. Post-mortem immunohistochemical analysis is the current reliable method of differentiating TDP-43 deposits in cortical tissue; no means of antemortem diagnosis exists in biofluids, let alone in plasma.

Methods: Here the multimer detection system (MDS) was used to quantify the oligomeric TDP-43 (o-TDP-43) concentrations in plasma of Korean SD patients (n = 16, 6 male, 10 female, ages 59-87).

A Microplate-Based Approach to Map Interactions between TDP-43 and α-Synuclein.

Trans-active response DNA-binding protein (TDP-43) is a multifunctional regulatory protein, whose abnormal deposition in neurons was linked to debilitating neurodegenerative diseases, such as amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Limbic-predominant age-related TDP-43 encephalopathy, and Alzheimer's disease with a secondary pathology. Several reports showed that TDP-43 proteinopathy as a comorbidity can form aggregates with other pathological proteins. The co-deposition of alpha synuclein and TDP-43 inclusions was previously reported in glial cells and by observing TDP-43 proteinopathy in Lewy body disease.

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation.

Background: Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia.

The influence of Aβ-dependent and independent pathways on TDP-43 proteinopathy in Alzheimer's disease: a possible connection to LATE-NC.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results from the accumulation of plaques by cleaved Aβ peptides as well as neurofibrillary tangles of tau proteins. This accumulation triggers a complex cascade of cytotoxic, neuroinflammatory, and oxidative stresses that lead to neuronal death throughout the progression of the disease. Much of research in AD focused on the 2 pathologic proteins.

Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases.

Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems.

Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer's Disease.

The bidirectional communication between the central nervous system (CNS) and the gut microbiota plays a pivotal role in human health. Increasing numbers of studies suggest that the gut microbiota can influence the brain and behavior of patients. Various metabolites secreted by the gut microbiota can affect the cognitive ability of patients diagnosed with neurodegenerative diseases.