Alzheimer´s disease is a chronic neurodegenerative disorder affecting millions of people worldwide, characterized by a progressive decline in cognitive functions. Factors involved in the pathogenesis of Alzheimer´s disease include metabolic alterations such as insulin resistance and hyperglycemia, both of which are also hallmarks of type-2 diabetes mellitus. The accumulation of β-amyloid peptid...

The way for explanation postischemic dementia processes has been one fraught with a wide range of complications and frequent revisions with a lack of a final clear solution. Data from animal models of brain ischemia and human ischemic brains studies have demonstrated an overexpression of amyloid precursor protein and increase production of a β-amyloid peptide. Restoration brain activity followi...

PRINCIPLES Amyloids are highly cross-β-sheet-rich aggregated states that confer protease resistance, membrane activity and multivalence properties to proteins, all essential features for the undesired preservation of food proteins transiting the gastrointestinal tract and causing type I allergy. METHODS Amyloid propensity of β-parvalbumin, the major fish allergen, was theoretically analysed a...

Islet amyloid accumulation is a hallmark of human type 2 diabetes (T2D). In contrast to human islet amyloid polypeptide (hIAPP), murine islet amyloid polypeptide (mIAPP) does not exhibit amyloidogenic propensity. Because autophagy is important in the clearance of amyloid-like proteins, we studied transgenic mice with β cell-specific expression of hIAPP to evaluate the contribution of autophagy ...

Heurling, K. 2015. Characterization of [F]flutemetamol binding properties. A β-amyloid PET imaging ligand. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1139. 74 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9356-1. The criteria for diagnosing Alzheimer’s disease (AD) have recently been revised to include the use of biomarkers for the in vi...

A major neuropathological hallmark of Alzheimer's disease is the deposition of amyloid plaques in the brains of affected individuals. Amyloid plaques mainly consist of fibrillar β-amyloid, which is a cleavage product of the amyloid precursor protein. The amyloid-cascade-hypothesis postulates Aβ accumulation as the central event in initiating a toxic cascade leading to Alzheimer's disease pathol...

Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological...

Abstract Background Amyloid-β is a major hallmark of Alzheimer's disease, and its pathology has been hypothesized as multiple organ syndrome that may also affect cardiac function. There are limited data on association plasma amyloid-β with dysfunction risk HF in the general population. Objective To determine amyloid-β40 (Aβ40) amyloid-β42 (Aβ42) echocardiographic measurements dysfunction, incid...

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 ac...

The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloi...