Clinicopathologic Correlations in a Large Alzheimer Disease Center Autopsy Cohort

Nelson, Peter T.; Jicha, Gregory A.; Schmitt, Frederick A.; Liu, Huaichen; Davis, Daron G.; Mendiondo, Marta S.; Abner, Erin L.; Markesbery, William R.

doi:10.1097/nen.0b013e31815c5efb

Cited by 263 publications

(183 citation statements)

References 83 publications

Supporting

Mentioning

163

Contrasting

Order By: Relevance

“…Although cognitively normal elderly may show variable neocortical AD-related pathology, in general, the number of isocortical tangles correlates best with the severity of cognitive impairment (Nelson et al, 2007;Nelson et al, 2009;Markesbery, 2010;Nelson et al, 2012). The pattern of gray matter loss associated with tangle pathology is an appropriate in vivo surrogate indicator of AD pathology (Whitwell et al, 2008).…”

Section: Specific Problems In the Diagnosis Of Alzheimer Diseasementioning

confidence: 99%

“…The pattern of gray matter loss associated with tangle pathology is an appropriate in vivo surrogate indicator of AD pathology (Whitwell et al, 2008). The predictive value of widespread tau pathology (Braak stages V-VI) for dementia is high (Nelson et al, 2007;Nelson et al, 2012), while others found that both diffuse and neuritic plaques, rather than tangles in neocortical regions distinguish nondemented and AD subjects with high sensitivity and specificity (McKeel et al, 2004). A recent study found that the amyloid stage that has progressed to involve the striatum is highly predictive of dementia .…”

Section: Specific Problems In the Diagnosis Of Alzheimer Diseasementioning

confidence: 99%

See 1 more Smart Citation

Challenges in the Neuropathological Diagnosis of Dementias

2013

IJN

View full text Add to dashboard Cite

Dementia, defined as deterioration in several cognitive domains, is a major public health problem that threatens to become the scourge of the 21th century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Consensus criteria for the diagnosis of different dementia disorders have recently been updated. Clinical diagnostic accuracy using revised research criteria and new chemical, imaging and genetic biomarkers ranges from 65 to 96% (for Alzheimer disease), with a sensitivity versus other dementias of 71 to 87% and specificity of 44 to 71%. Morphological assessment, using immunohistochemistry, molecular biological and genetic methods and based on homogenous definitions, harmonized inter-laboratory methods and assessment standards, can achieve a diagnosis/classificaion in almost 99%, without, however, clarifying the etiology of most of these disorders. The new National Institute on Aging-Alzheimer Association (ABC) guidelines for pathological diagnosis of Alzheimer disease combine β-amyloid plaque phases, Braak neurofibrillary and neuritic plaque scores, also considering other pathologies. Major difficulties arise from recent separation of distinct clinico-pathological subtypes (tangle-and plaque intensive, tangle predominant, limbic-predominant and -sparing) from classical Alzheimer disease. Revised research criteria are available for dementia with Lewy bodies, Parkinson disease-dementia, frontotemporal lobe degeneration, vascular cognitive impairment/dementia, prion diseases, and other neurodegenerative dementias. However, due to considerable overlap between various neurodegenerative proteinopathies and cases with mixed pathologies, human postmortem studies entail numerous biases that affect both their general applicability and the validity of correlations. Although most neurodegenerative dementias are incurable at present, concerted prospective clinico-pathological studies using validated protocols and data fusion are required to overcome the limitations of the current diagnostic framework as a basis for efficient new therapy options.

show abstract

Section: Specific Problems In the Diagnosis Of Alzheimer Diseasementioning

confidence: 99%

Section: Specific Problems In the Diagnosis Of Alzheimer Diseasementioning

confidence: 99%

Challenges in the Neuropathological Diagnosis of Dementias

2013

IJN

View full text Add to dashboard Cite

show abstract

“…Such DNA damage could potently lead to the loss of ribosomal DNA copies. Alzheimer's Disease Center cohort and were followed for at least 2 years before death [53]. The follow up included annual Minimental State Examination as well as neurological and physical examinations.…”

Section: Introductionmentioning

confidence: 99%

“…The Minimental State Examination score closest to death was used as an indicator of overall cognitive status. During autopsy (usually 5 or less hours after death), tissue samples including parietal cortex and cerebellum were processed for neuropathological evaluations or flash-frozen in liquid nitrogen and stored at -80°C, as described previously [53,54]. All included Dementia with Lewy Bodies subjects met the clinical and histopathological criteria for diagnosis of Dementia with Lewy Bodies [55].…”

Section: Introductionmentioning

confidence: 99%

Neurodegeneration-associated instability of ribosomal DNA.

Hallgren¹

View full text Add to dashboard Cite

Homologous recombination-mediated instability of the repetitively organized ribosomal DNA has been proposed as a mediator of cell senescence in yeast triggering the DNA damage response. High individual variability in the content of human ribosomal DNA suggests that this genomic region remained relatively unstable throughout evolution. Therefore, quantitative real time PCR was used to determine the genomic content of ribosomal DNA in post mortem samples of parietal cortex from 14 young and

show abstract

“…According to Braak et al 9 , the presence of tau deposits is classified in six stages, from I to VI, beginning with the transentorhinal region (stage I) and progressing until stage VI with severe pathology of the isocortex. Late phases of the disease cause recognizable symptoms and have been correlated with the clinical manifestations of AD 6,10,11 . However, studies of these phases have been laden with difficulties, due to the large number of altered nerve cells.…”

mentioning

confidence: 99%

Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study

Oliveira

Neto

Fonseca

et al. 2015

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

With the increase in life expectancy in Brazil, concerns have grown about the most prevalent diseases in elderly people. Among these diseases are neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Protein deposits related to the development of these diseases can pre-date the symptomatic phases by years. The tau protein is particularly interesting: it might be found in the brainstem and olfactory bulb long before it reaches the limbic cortex, at which point symptoms occur. Of the 14 brains collected in this study, the tau protein was found in the brainstems of 10 (71.42%) and in olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of Alzheimer’s disease (AD), 6 presented tau deposits in some region of the brainstem. Our data support the idea of the presence of tau protein in the brainstem and olfactory bulb in the earliest stages of AD.

show abstract

Clinicopathologic Correlations in a Large Alzheimer Disease Center Autopsy Cohort

Cited by 263 publications

References 83 publications

Challenges in the Neuropathological Diagnosis of Dementias

Challenges in the Neuropathological Diagnosis of Dementias

Neurodegeneration-associated instability of ribosomal DNA.

Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study

Contact Info

Product

Resources

About