Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques

Katzman, Robert; Terry, Robert D.; DeTeresa, Richard; Brown, Theodore J.; Davies, Peter; Fuld, Paula Altman; Renbing, Xiong; Peck, Arthur

doi:10.1002/ana.410230206

Cited by 1,078 publications

(685 citation statements)

References 15 publications

Supporting

Mentioning

616

Contrasting

Unclassified

Order By: Relevance

“…By proposing that the primary toxic species are the early aggregates, this theory also provides a plausible explanation for the lack of correlation between the extent of deposition of mature fibrils in the form of amyloid plaques in the diseased brain and the severity of clinical symptoms. 12 …”

Section: Causes Of Amyloid Pathologymentioning

confidence: 99%

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

2008

View full text Add to dashboard Cite

The in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors may be critical parts of a quality control system to protect the body against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. Keywords: Extracellular chaperones, receptor-mediated endocytosis, amyloid, protein quality control, aggregate toxicity, fibril formation word statement (for Contents list) plus graphic (note -colour version of below graphic provided separately)Newly identified abundant extracellular chaperones (ECs) may protect the body against dangerously hydrophobic proteins/peptides. This review proposes that ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. SUMMARYThe in vivo formation of fibrillar proteinaceous deposits called amyloid is associated with more than 40 serious human diseases, collectively referred to as protein deposition diseases. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is presented suggesting an important regulatory role for ECs in amyloid formation and disposal in the body. A model is presented which proposes that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific cell receptors for uptake and subsequent degradation. Thus ECs and their receptors may be critical parts of a quality control system to protect the body against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

show abstract

Section: Causes Of Amyloid Pathologymentioning

confidence: 99%

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

2008

View full text Add to dashboard Cite

show abstract

“…The neural correlate of CR can be conceived in at least two ways [7••]. First, bigger brains may tolerate more loss before exhibiting impaired function because of higher number of healthy synapses or neurons, resulting in increased number of remaining available ones when a certain percentage of them are affected by a pathologic process [1]. This can be seen as a passive role of CR, which focuses on the "hardware" of the brain.…”

Section: Possible Mechanismsmentioning

confidence: 99%

“…For example, Katzman et al [1,2] described cases of cognitively normal, elderly women who were discovered to have advanced AD pathology in their brains at death. They speculated these women did not express the clinical features of AD because their brains were larger than average.…”

Section: Introductionmentioning

confidence: 99%

Cognitive reserve: Implications for diagnosis and prevention of Alzheimer’s disease

Scarmeas

Stern

2004

Curr Neurol Neurosci Rep

210

132

View full text Add to dashboard Cite

Epidemiologic evidence suggests that higher occupational attainment and education, as well as increased participation in intellectual, social, and physical aspects of daily life, are associated with slower cognitive decline in healthy elderly and may reduce the risk of incident Alzheimer's disease (AD). There is also evidence from structural and functional imaging studies that patients with such life experiences can tolerate more AD pathology before showing signs of clinical dementia. It has been hypothesized that such aspects of life experience may result in functionally more efficient cognitive networks and, therefore, provide a cognitive reserve that delays the onset of clinical manifestations of dementia. In this article, we review some of the relevant literature of the noted associations between markers of cognitive reserve and AD and discuss the possible mechanisms that may explain these associations.

show abstract

“…Given that these subjects presented larger brain volumes than the average, the associated notion of “brain reserve” (BR) arose [Katzman, 1993]; with brain size and neuronal numbers constituting standard proxies for BR [Katzman et al, 1988; Mortimer et al, 1982, 2003; Satz et al, 2011]. According to the model, brain size determines the amount of damage that can be sustained before it leads to some clinical expression.…”

Section: Introductionmentioning

confidence: 99%

The functional connectome of cognitive reserve

Marques

Moreira

Magalhães

et al. 2016

Human Brain Mapping

View full text Add to dashboard Cite

Cognitive Reserve (CR) designates the brain's capacity to actively cope with insults through a more efficient use of its resources/networks. It was proposed in order to explain the discrepancies between the observed cognitive ability and the expected capacity for an individual. Typical proxies of CR include education and Intelligence Quotient but none totally account for the variability of CR and no study has shown if the brain's greater efficiency associated with CR can be measured. We used a validated model to estimate CR from the residual variance in memory and general executive functioning, accounting for both brain anatomical (i.e., gray matter and white matter signal abnormalities volume) and demographic variables (i.e., years of formal education and sex). Functional connectivity (FC) networks and topological properties were explored for associations with CR. Demographic characteristics, mainly accounted by years of formal education, were associated with higher FC, clustering, local efficiency and strength in parietal and occipital regions and greater network transitivity. Higher CR was associated with a greater FC, local efficiency and clustering of occipital regions, strength and centrality of the inferior temporal gyrus and higher global efficiency. Altogether, these findings suggest that education may facilitate the brain's ability to form segregated functional groups, reinforcing the view that higher education level triggers more specialized use of neural processing. Additionally, this study demonstrated for the first time that CR is associated with more efficient processing of information in the human brain and reinforces the existence of a fine balance between segregation and integration. Hum Brain Mapp 37:3310–3322, 2016.. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

show abstract

Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques

Cited by 1,078 publications

References 15 publications

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity

Cognitive reserve: Implications for diagnosis and prevention of Alzheimer’s disease

The functional connectome of cognitive reserve

Contact Info

Product

Resources

About