Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.

Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

The amyloid state of proteins in human diseases

Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.

http://science.sciencemag.org/content/sci/313/5794/1781.full.pdf

Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host.

Mind how you go: The current strategies for the development of therapies for Alzheimer's disease are very diverse. Particular attention is given to the search for inhibitors (see picture for two examples) of the proteolytic enzyme beta- and gamma-secretase, which inhibits the cleavage of the amyloid precursor proteins into amyloid beta peptides, from which the disease-defining deposits of plaque in the brains of Alzheimer's patients originates.Research on senile dementia and Alzheimer's disease covers an extremely broad range of scientific activities. At the recent international meeting of the Alzheimer's Association (ICAD 2008, Chicago) more than 2200 individual scientific contributions were presented. The aim of this Review is to give an overview of the field and to outline its main areas, starting from behavioral abnormalities and visible pathological findings and then focusing on the molecular details of the pathology. The "amyloid hypothesis" of Alzheimer's disease is given particular attention, since the majority of the ongoing therapeutic approaches are based on its theoretical framework.

Alzheimer's Disease: From Pathology to Therapeutic Approaches

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease The brain is particularly vulnerable to oxidative damage induced by unregulated redox-active metals such as copper and iron, and the brains of AD patients display evidence of metal dyshomeostasis and increased oxidative stress The colocalisation of copper and amyloid β (Aβ) in the glutamatergic synapse during NMDA-receptor-mediated neurotransmission provides a microenvironment favouring the abnormal interaction of redox-potent Aβ with copper under conditions of copper dysregulation thought to prevail in the AD brain, resulting in the formation of neurotoxic soluble Aβ oligomers Interactions between Aβ oligomers and copper can further promote the aggregation of Aβ, which is the core component of extracellular amyloid plaques, a central pathological hallmark of AD Copper dysregulation is also implicated in the hyperphosphorylation and aggregation of tau, the main component of neurofibrillary tangles, which is also a defining pathological hallmark of AD Therefore, tight regulation of neuronal copper homeostasis is essential to the integrity of normal brain functions Therapeutic strategies targeting interactions between Aβ, tau and metals to restore copper and metal homeostasis are discussed

Copper in the brain and Alzheimer's disease.

The structural changes of Alzheimer's disease (AD) include a widespread alteration of neuronal cell processes in addition to senile plaques and neurofibrillary tangles. Since the antigenic characteristics of these abnormal neurites are similar to those of the abnormal neurites associated with the senile plaques, the question has been raised as to whether the widespread neuritic alteration is secondary to the deposition of amyloid. To answer this question, we examined brains from 2 subjects with a longer-lasting form of subacute sclerosing panencephalitis (SSPE) characterized by the presence of numerous neurofibrillary tangles but no senile plaques, 3 subjects with AD, and 2 age-matched controls. Light and electron immunocytochemical analyses revealed that abnormal neurites are present diffusely in SSPE cerebral cortex in the absence of amyloid deposits. These abnormal neurites were qualitatively identical to the widespread abnormal neurites of AD. The abnormal neurites, in contrast to the neurites of control brains, immunoreacted with antibodies to tau and ubiquitin. These distinctive antigenic features were due to the presence in these abnormal neurites of straight filaments, 14 to 16 nm in diameter, mixed with a few paired helical filaments. The spatial distribution of the widespread neuritic alteration correlated with that of neurofibrillary tangles in both conditions, but not with that of senile plaques in AD. The present findings demonstrate that a diffuse alteration of neurites similar to that present in AD takes place independently of the deposition of amyloid in SSPE, and they are consistent with the hypothesis that in AD, also, this alteration is not secondary to the deposition of amyloid.(ABSTRACT TRUNCATED AT 250 WORDS)

The widespread alteration of neurites in alzheimer disease may be unrelated to amyloid deposition: 118

/pdf/erratum-autophagocytosis-of-mitochondria-is-prominent-in-58w2i4wods.pdf

Erratum: Autophagocytosis of mitochondria is prominent in Alzheimer disease (Journal of Neuropathology and Experimental Neurology (2007) 66, (525-532))

Alzheimer disease paired helical filament fractions contain insoluble tubulin: 160

Effect of a Polymorphism on the Pathogenic 178Asn Mutation in the Prion Protein Gene

Ubiquitin Reactive Neurites In Cerebral Cortex Of Huntingtonʼs Chorea: do they correlate with dementia?

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

M. Tabaton

Author Tools

Chat about Author