The discovery of Alzheimer's disease

Hippius, Hanns; Neundörfer, Gabriele

doi:10.31887/dcns.2003.5.1/hhippius

Cited by 268 publications

(147 citation statements)

References 12 publications

(9 reference statements)

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“…The hypothesis of similarity in the underlying mechanisms for the shared white matter deficits between AD and SZ is still a subject to debate. Contemporary medicine has largely dismissed Kraepelin’s definition of SZ as premature dementia 61 due to the lack of evidence for neurodegenerative cognitive decline in most SZ patients. 6 The lack of amyloid-β and τ-protein pathologies in most SZ postmortem studies further suggests nonoverlapping pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

A White Matter Connection of Schizophrenia and Alzheimer’s Disease

Kochunov

Zavaliangos‐Petropulu

Jahanshad

et al. 2020

Schizophrenia Bulletin

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Schizophrenia (SZ) is a severe psychiatric illness associated with an elevated risk for developing Alzheimer’s disease (AD). Both SZ and AD have white matter abnormalities and cognitive deficits as core disease features. We hypothesized that aging in SZ patients may be associated with the development of cerebral white matter deficit patterns similar to those observed in AD. We identified and replicated aging-related increases in the similarity between white matter deficit patterns in patients with SZ and AD. The white matter “regional vulnerability index” (RVI) for AD was significantly higher in SZ patients compared with healthy controls in both the independent discovery (Cohen’s d = 0.44, P = 1·10–5, N = 173 patients/230 control) and replication (Cohen’s d = 0.78, P = 9·10–7, N = 122 patients/64 controls) samples. The degree of overlap with the AD deficit pattern was significantly correlated with age in patients (r = .21 and .29, P < .01 in discovery and replication cohorts, respectively) but not in controls. Elevated RVI-AD was significantly associated with cognitive measures in both SZ and AD. Disease and cognitive specificities were also tested in patients with mild cognitive impairment and showed intermediate overlap. SZ and AD have diverse etiologies and clinical courses; our findings suggest that white matter deficits may represent a key intersecting point for these 2 otherwise distinct diseases. Identifying mechanisms underlying this white matter deficit pattern may yield preventative and treatment targets for cognitive deficits in both SZ and AD patients.

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Section: Discussionmentioning

confidence: 99%

A White Matter Connection of Schizophrenia and Alzheimer’s Disease

Kochunov

Zavaliangos‐Petropulu

Jahanshad

et al. 2020

Schizophrenia Bulletin

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“…Alzheimer’s disease (AD) was first described and diagnosed by Dr. Alois Alzheimer in 1906 [ 1 ]. According to World Health Organization (WHO), AD is the most common cause of dementia, accounting for as many as 60 ~ 70% of senile dementia cases and affecting 47.5 million people worldwide in 2015 [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Drug candidates in clinical trials for Alzheimer’s disease

2017

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Alzheimer’s disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD result in a progressive and significant loss of cognitive and behavioral function. Current AD medications, memantine and acetylcholinesterase inhibitors (AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, but they are not curative. Since 2003, no new drugs have been approved for the treatment of AD. This article focuses on the current research in clinical trials targeting the neuropathological findings of AD including acetylcholine response, glutamate transmission, Aβ clearance, tau protein deposits, and neuroinflammation. These investigations include acetylcholinesterase inhibitors, agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau protein, as well as anti-inflammation compounds. Ongoing Phase III clinical trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. Using small molecules blocking 5-HT6 serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials. We here systemically review the findings from recent clinical trials to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD.

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“…Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized clinically by cognitive and memory dysfunction, accompanied by classical hallmark pathologies such as intraneuronal neurofibrillary tangles (NFTs) and extracellular amyloid plaques [ 1 - 3 ]. NFTs are enriched with hyperphosphorylated microtubule-associated protein tau (MAPT) [ 2 ], which can be phosphorylated by multiple protein kinases.…”

Section: Introductionmentioning

confidence: 99%

Trafficking regulation of proteins in Alzheimer’s disease

Jiang

Zhang

et al. 2014

Mol Neurodegeneration

123

114

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The β-amyloid (Aβ) peptide has been postulated to be a key determinant in the pathogenesis of Alzheimer’s disease (AD). Aβ is produced through sequential cleavage of the β-amyloid precursor protein (APP) by β- and γ-secretases. APP and relevant secretases are transmembrane proteins and traffic through the secretory pathway in a highly regulated fashion. Perturbation of their intracellular trafficking may affect dynamic interactions among these proteins, thus altering Aβ generation and accelerating disease pathogenesis. Herein, we review recent progress elucidating the regulation of intracellular trafficking of these essential protein components in AD.

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The discovery of Alzheimer's disease

Cited by 268 publications

References 12 publications

A White Matter Connection of Schizophrenia and Alzheimer’s Disease

A White Matter Connection of Schizophrenia and Alzheimer’s Disease

Drug candidates in clinical trials for Alzheimer’s disease

Trafficking regulation of proteins in Alzheimer’s disease

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