Accumulation of the amyloid-beta (Aβ) peptide is a central factor in Alzheimer's disease (AD) pathogenesis as supported by continuing evidence. This review concisely summarizes this evidence supporting a critical role for Aβ in AD before discussing the clearance of this peptide. Mechanisms of clearance of Aβ are critical for preventing pathological elevations in Aβ concentration. Direct degrada...

The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation of beta-amyloid (Aβ) and hyperphosphorylated tau protein into neurotoxic deposits. Aβ aggregation has been suggested as the critical early inducer, driving the disease progression. However, the factors that promote neurotoxic Aβ aggregation remain elusive. Imaging mass spectrometry (IMS...

Mitochondrial dysfunction is a hallmark of amyloid-beta(Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). The recent emphasis on the intracellular biology of Aβ and its precursor protein (AβPP) has led researchers to consider the possibility that mitochondria-associated and/or intramitochondrial Aβ may directly cause neurotoxicity. In this paper, we will outline current knowledge of th...

A hallmark pathological feature of Alzheimer's disease (AD) is the accumulation of extracellular plaques composed of the amyloid-beta (Aβ) peptide. Thus, classically experiments were designed to examine Aβ toxicities within the central nervous system (CNS) from the extracellular space. However, a significant amount of evidence now suggests that intraneuronal accumulation of Aβ is neurotoxic and...

Numerous studies have shown that autophagy failure plays a critical role in the pathogenesis of Alzheimer's disease, including increased expression of beta-amyloid (Aβ) protein and the dysfunction of Aβ clearance. To further evaluate the role of autophagy in Alzheimer's disease, the present study was implemented to investigate the effects of autophagy on α-secretase, β-secretase, or γ-secretase...

Gangliosides are important players for controlling neuronal function and are directly involved in AD pathology. They are among the most potent stimulators of Aβ production, are enriched in amyloid plaques and bind amyloid beta (Aβ). However, the molecular mechanisms linking gangliosides with AD are unknown. Here we identified the previously unknown function of the amyloid precursor protein (APP...

Extracellular and intraneuronal accumulation of amyloid-beta (Aβ) peptide aggregates in the brain has been hypothesized to play an important role in the neuropathology of Alzheimer's Disease (AD). The main Aβ variants detected in the human brain are Aβ1-40 and Aβ1-42, however a significant proportion of AD brain Aβ consists also of N-terminal truncated species. Pyroglutamate-modified Aβ peptide...

List of abbreviations Alzheimer’s Disease, AD; Amyloid Precursor Protein, APP; Beta-Amyloid, Aβ; Bovine Spongiform Encephalopathy, BSE; Creutzfeldt-Jakob Disease, CJD; Central Nervous System, CNS; Immunofluorescence, IF; Immunoprecipitation, IP; Enzyme Linked Immunosorbent Assay, ELISA; Huntingtin, Htt; Huntington’s Disease, HD; Immunohistochemistry, IHC; Luminescent Conjugated Oligothiophenes,...

In Alzheimer’s disease (AD) two aberrant proteins amyloid plaques (Aβ) and Neurofibrillary tangles (NFTs) have been identified. Aβ peptide is produced from soluble amyloid precursor protein (SAPP) as a result of two sequential proteolysis steps by β-secretase [beta-site Amyloid Precursor Protein Cleaving Enzyme (BACE)] then γ-secretase. NFTs, are made up of several proteins but primarily hypoph...

BACKGROUND Amyloid beta (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, serum Aβ levels could be associated with depressive symptoms. The aim of this study was to investigate whether serum Aβ levels are associated with depressive symptoms and/or cognitive function in community-dwelling elderly individuals. ME...