SPECIFIC AIMS We have examined the hypothesis that small molecular weight compounds capable of inhibiting the aggregation of the beta-amyloid peptide (Aβ) could protect neurons from the toxic effect of Aβ and prevent cerebral amyloid deposition. The anti-aggregating and neuroprotective effects of nitrophenols were investigated in vitro using primary cultures of rat hippocampal neurons, and the ...

the progression of Alzheimer’s disease. (AD), and the presence of amyloid plaques in the brain is an invariant feature of the disease. The primary component of these neuritic plaques is the amyloid-β (Aβ) protein, and its aggregation into plaques has been proposed to be a cause of AD neurodegeneration (Hardy and Higgins, 1992). The amyloid cascade hypothesis continues to be controversial, and t...

β-Amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer disease (AD) and possibly vascular dementia. We investigated the joint association of midlife BP and Aβ peptide levels with the risk for late-life AD and vascular dementia. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Pro...

The pathological signature of Alzheimer’s disease is the deposition of β-amyloid protein (Aβ). Its cleavage products, such as Aβ40 and Aβ42, form amyloid fibrils and plaques in the brains of affected individuals. Compounds that have affinity for Aβ have the ability to prevent neurotoxicity by inhibiting aggregation of amyloid fibrils. In addition, these molecules can also serve to quantify amyl...

In addition to the prototypic amyloid-β (Aβ) peptides Aβ1-40 and Aβ1-42 , several Aβ variants differing in their amino and carboxy termini have been described. Synthetic availability of an Aβ variant is often the key to study its role under physiological or pathological conditions. Herein, we report a protocol for the efficient solid-phase peptide synthesis of the N-terminally elongated Aβ-pept...

In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: Using the experimental structures of Aβ amyloid fibrils and all-atom molecular dynamics, we study the force-induced unbindin...

The presence of amyloid aggregates of the 42 amino acid peptide of amyloid beta (Aβ42) in the brain is the characteristic feature of Alzheimer's disease (AD). Amyloid beta (Aβ deposition is also found in muscle fibers of individuals affected by inclusion body myositis (sIBM), a rare muscular degenerative disease affecting people over 50. Both conditions are presently lacking an effective therap...

The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studie...

One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological loc...

OBJECTIVE To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. METHODS Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET β-amyloid (Aβ) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on th...