Alzheimer's disease (AD) is a neurodegenerative disease, one of whose major pathological hallmarks is the accumulation of amyloid plaques comprised of aggregated β-amyloid (Aβ) peptides. It is now recognized that soluble Aβ oligomers may lead to synaptic dysfunctions early in AD pathology preceding plaque deposition. Aβ is produced by a sequential cleavage of amyloid precursor protein (APP) by ...

Assembly of amyloid-beta peptide (Aβ) into cytotoxic oligomeric and fibrillar aggregates is believed to be a major pathologic event in Alzheimer's disease (AD) and interfering with Aβ aggregation is an important strategy in the development of novel therapeutic approaches. Prior studies have shown that the double N-methylated analogue of islet amyloid polypeptide (IAPP) IAPP-GI, which is a confo...

Amyloid-beta peptide (Aβ) aggregation is one of the hallmarks of Alzheimer's disease (AD), and metal ions such as Cu(ii) have been proposed to play a role in amyloid formation and the onset of this progressive neurodegenerative disorder. This study reports the design and characterization of a novel bifunctional non-natural tetrapeptide, Met-Asp-d-Trp-Aib, that is capable of binding copper, comp...

According to the "amyloid hypothesis," accumulation of amyloid beta (Aβ) peptides in the brain is linked to the development of Alzheimer's disease. The aims of this investigation were to develop a model for the age-dependent amyloid accumulation and to quantify the age- and treatment-duration-dependent efficacy of the γ-secretase inhibitor MRK-560 in the Tg2576 transgenic mouse model of amyloid...

Endothelial cells of brain capillaries forming the blood-brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid-β (Aβ) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of...

In Alzheimer's disease (AD), amyloid-β (Aβ) deposits are frequently surrounded by activated microglia but the precise role of these cells in disease progression remains unclear. The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity. To study the specific effects of microglia activation on amyloid pathology in vivo, we crossbred mice lackin...

Extensive data supports the amyloid cascade hypothesis, which states that Alzheimer's disease (AD) stems from neurotoxic forms of the amyloid-beta (Aβ) peptide. But the poor correlation between Aβ plaques and neurodegeneration/cognitive impairment, the spaciotemporal disparity between Aβ and tau pathology, and the disappointing results following several large clinical trials using Aβ-targeting ...

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, responsible for nearly two-thirds of all dementia cases. In this review, we report potential AD treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically inhibition polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk biosurfaces. We discuss how thes...

Although central nervous system-resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer's disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in ...

AD (Alzheimer’s disease) is a neurodegenerative disorder characterized by self-assembly and amyloid formation of the 39–43 residue long Aβ (amyloid-β)-peptide. The most abundant species, Aβ(1–40) and Aβ(1–42), are both present within senile plaques, but Aβ(1–42) peptides are considerably more prone to selfaggregation and are also essential for the development of AD. To understand the molecular ...