The case described by Alois Alzheimer in 1911

Möller, H.-J.; Graeber, Manuel B.

doi:10.1007/s004060050027

Cited by 164 publications

(51 citation statements)

References 43 publications

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“…Alois Alzheimer first described the disease that bears his name in a lecture in 1906 after studying the case of a 51-year-old woman, Auguste Deter, who was admitted to the Frankfurt Asylum suffering from severe dementia (Möller and Graeber 1998). At the time, her case was a curiosity, and it is now evident that she was suffering from a rare early-onset form of AD.…”

Section: The Increasing Prevalence Of Protein-misfolding Disordersmentioning

confidence: 99%

The Amyloid Phenomenon and Its Links with Human Disease

Dobson

2017

Cold Spring Harb Perspect Biol

128

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The ability of normally soluble proteins to convert into amyloid fibrils is now recognized to be a generic phenomenon. The overall cross-b architecture of the core elements of such structures is closely similar for different amino acid sequences, as this architecture is dominated by interactions associated with the common polypeptide main chain. In contrast, the multiplicity of complex and intricate structures of the functional states of proteins is dictated by specific interactions involving the variable side chains, the sequence of which is unique to a given protein. Nevertheless, the side chains dictate important aspects of the amyloid structure, including the regions of the sequence that form the core elements of the fibrils and the kinetics and mechanism of the conversion process. The formation of the amyloid state of proteins is of particular importance in the context of a range of medical disorders that include Alzheimer's and Parkinson's diseases and type 2 diabetes. These disorders are becoming increasingly common in the modern world, primarily as a consequence of increasing life spans and changing lifestyles, and now affect some 500 million people worldwide. This review describes recent progress in our understanding of the molecular origins of these conditions and discusses emerging ideas for new and rational therapeutic strategies by which to combat their onset and progression.

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Section: The Increasing Prevalence Of Protein-misfolding Disordersmentioning

confidence: 99%

The Amyloid Phenomenon and Its Links with Human Disease

Dobson

2017

Cold Spring Harb Perspect Biol

128

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“…As a progressive, disabling and incurable disease, patients die within average of 10 years after its installation [7]. The age is its main risk factor, with a prevalence of 0.7% among individuals 60-65 years of age and about 40% in the age groups above 90 years [8, 9].…”

Section: Socio-economic Impact and Prevalence Of Alzheimer's Diseasementioning

confidence: 99%

Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer’s Disease

Dias

Viegas²

2014

155

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Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a multi-faceted pathogenesis. So far, the therapeutic paradigm “one-compound-one-target” has failed and despite enormous efforts to elucidate the pathophysiology of AD, the disease is still incurable. The multiple factors involved in AD include amyloid aggregation to form insoluble neurotoxic plaques of Aβ, hyperphosphorylation of tau protein, oxidative stress, calcium imbalance, mitochondrial dysfunction and deterioration of synaptic transmission. These factors together, accentuate changes in the CNS homeostasis, starting a complex process of interconnected physiological damage, leading to cognitive and memory impairment and neuronal death. A recent approach for the rational design of new drug candidates, also called multitarget-directed ligand (MTDL) approach, has gained increasing attention by many research groups, which have developed a variety of hybrid compounds acting simultaneously on diverse biological targets. This review aims to show some recent advances and examples of the exploitation of MTDL approach in the rational design of novel drug candidate prototypes for the treatment of AD.

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“…Genotyping of tissue from the original histological slides from Deter's brain autopsy revealed she likely had PS1-linked FAD [9] [10]. In contrast to the original “amyloid cascade” hypothesis that Aβ plaques drive the neuropathological cascade leading to dementia [11], Dr. Alzheimer wrote “...the plaques are not the cause of senile dementia, but only an accompanying feature of senile involution of the central nervous system” [12] [13]. In 1999, Mesulam [14] wrote, “It seems as if the Aβ plaques appear at the wrong time and in the wrong places with respect to the clinical dementia and there is little evidence that they cause the NFT”.…”

Section: Introductionmentioning

confidence: 99%

Molecular and cellular pathophysiology of preclinical Alzheimer’s disease

Mufson

Ikonomović

Counts

et al. 2016

Behavioural Brain Research

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Although the two pathological hallmarks of Alzheimer's disease (AD), senile plaques composed of amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau, have been studied extensively in postmortem AD and relevant animal and cellular models, the pathogenesis of AD remains unknown, particularly in the early stages of the disease where therapies presumably would be most effective. We and others have demonstrated that Aβ plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia. In this regard, aged people with no cognitive impairment (NCI), mild cognitive impairment (MCI, a presumed prodromal AD transitional state), and AD all present at autopsy with varying levels of pathological hallmarks. Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Aβ plaques. However, correlations are even higher between cognitive decline and synaptic loss. In this review, we illustrate relevant clinical pathological research in preclinical AD and throughout the progression of dementia in several areas including Aβ and tau pathobiology, single population expression profiling of vulnerable hippocampal and basal forebrain neurons, neuron plasticity, neuroimaging, cerebrospinal fluid (CSF) biomarker studies and their correlation with antemortem cognitive endpoints. In each of these areas, we provide evidence for the importance of studying the pathological hallmarks of AD not in isolation, but rather in conjunction with other molecular, cellular, and imaging markers to provide a more systematic and comprehensive assessment of the multiple changes that occur during the transition from NCI to MCI to frank AD.

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The case described by Alois Alzheimer in 1911

Cited by 164 publications

References 43 publications

The Amyloid Phenomenon and Its Links with Human Disease

The Amyloid Phenomenon and Its Links with Human Disease

Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer’s Disease

Molecular and cellular pathophysiology of preclinical Alzheimer’s disease

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