Preclinical AD Workgroup staging: pathological correlates and potential challenges

Jicha, Gregory A.; Abner, Erin L.; Schmitt, Frederick A.; Kryscio, Richard J.; Riley, Kathryn; Cooper, Gregory; Stiles, Nancy; Mendiondo, Marta S.; Smith, Charles D.; Eldik, Linda J. Van; Nelson, Peter T.

doi:10.1016/j.neurobiolaging.2011.02.018

Cited by 62 publications

(53 citation statements)

References 114 publications

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“…Dementia with Lewy bodies (DLB), frontotemporal degeneration (FTD), vascular dementia, dementia with Parkinson's disease, are other forms of this class of neurological disorder. Moreover, a significant proportion of dementia patients have mixed pathology [10][11][12]. Due to the heterogeneity of dementia pathology and complexity of AD pathogenesis, therefore, multiple biomarkers with high sensitivity and specificity to detect AD are needed.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease

Kang

Vanderstichele²,

Trojanowski

et al. 2012

Methods

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Section: Introductionmentioning

confidence: 99%

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease

Kang

Vanderstichele²,

Trojanowski

et al. 2012

Methods

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“…Algorithms for the molecular-pathologic classification of sporadic (nongenetic/nonhereditary) forms of neurodegenerative dementias have been proposed [77,78,306]. However, due to variable overlap, these changes may fail to distinguish between cognitively intact aged subjects from those with MCI or preclinical or mild AD [4,8,92,307,308]. These latter groups show a wide variety in intensity and pattern of AD-related lesions and other (vascular) pathologies [230,302].…”

Section: Discussionmentioning

confidence: 99%

Neuropathology of Dementia Disorders

Jellinger¹

2014

J Alzheimers Dis Parkinsonism

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IntroductionDementia, encompassing deficits in several cognitive domains that are severe enough to interfere with daily functioning [1], in the new DSM V classification is classified within the broad category of major neurocognitive disorders, proposing specific criteria for the various etiologies [2]. Previously defined as the manifestation of deteriorating brain functions over time due to cell deaths in the brain caused by neurodegeneration or any other disease [3], according to recent research dementia is not primarily caused by neuronal cell death/loss, but by dysfunction and loss of synapses [4] in AD [5] and in α-synucleinopathies [6]. Other causes include cholinergic neuronal and axonal abnormalities [7,8], as well as pre-and postsynaptic cortical cholinergic deficits also occurring in early AD [9]. These changes due to disconnection of major nervous circuitries causing default networks [10][11][12][13] have been demonstrated in vivo in early AD [14], suggesting that disease progress is transmitted by neuronal pathways [15]. A prionlike spread of misfolded protein aggregates in the pathogenesis and progression of neurodegeneration is a hot spot of discussion [16][17][18][19][20][21].Both the prevalence and incidence of dementia increase exponentially with age. In 2010, 35.6 million people worldwide lived with dementia, with around 8 million new cases every year. Numbers are expected to double or triple every 5-10 years, to 135 millions in 2050, 16 millions in Europe. In 2010, 58% of all demented people lived in low-cost countries, with their proportion anticipated to rise to 71% in 2050 [22]. According to recent data from China the incidence of dementia was 9.87/1000 person years and the median standardised mortality ratio was 1.94:1 [23]. With the disproportional growth of the elderly population, dementia has become a major public health and socio-economic problem that threatens to become the scourge of our century. The total costs for dementia were US$ 604 billion in 2010 worldwide, up to 70% for social care alone [24], total payments for AD for 2013 were expected to be $ 203 billion in USA alone, not included contributions of unpaid caregivers [25]. Neuropathology of Dementia DisordersKurt A Jellinger* Institute of Clinical Neurobiology, Kenyongasse 18, A 1070, Vienna, Austria AbstractDementia, being not a specific disease but a syndrome characterized by deficits in several cognitive domains, is a major public health and socio-economic problem of our century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Despite updated concensus criteria for the clinical diagnosis of the major neurodegenerative disorders and new biomarkers, the diagnostic accuracy ranges from 65 to 96% (for Alzheimer's disease /AD), with a sensitivity versus other dementias of around 85.4% and a specificity of up to 77.7%. Pathologic assessment, using genetic and molecular biological methods, based on homogenous definitions, harmonized interlaboratory and assessment standards, can achiev...

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“…These methods of automated quantitative assessment, used in routine neuropathological diagnosis, provide a rough estimation of the amount of pathologies present in the brain. However, due to considerable overlap, these changes may fail to distinguish between cognitively intact subjects from those with preclinical disorders 53,54 . Additional challenges arise from the frequent coexistence of various pathologies in the aging brain which may have additive or synergistic effects (Figure 1) …”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Cerebral Multimorbidity in Aging

Jellinger¹

2016

J Neurol Neuromedicine

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The aging brain is characterized by the simultaneous presence of multiple pathologies, and the prevalence of multi-morbidity increases with age. Large clinico-pathological correlative studies have shown that in brains of both cognitively intact and impaired aged subjects, the presence of a single disease is a rare finding, while most brains show neurodegenerative, cerebrovascular and other pathologies, which frequently have been missed clinically and may even be difficult to identify at postmortem examination. Since both clinical and autopsy studies differ in selection and classification criteria and in the applied evaluation methods, irrespective of the clinical symptoms, the reported frequency of cerebral pathologies varies considerably. The frequent co-occurrence of different pathologies indicates their mutual interaction in order to promote cognitive decline and other clinical symptoms. These facts have also implications for improvement of clinical diagnosis and prognosis, for the development of specific biomarkers, preventive strategies, and therapeutic targets for cerebral multi-morbidity.

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Preclinical AD Workgroup staging: pathological correlates and potential challenges

Cited by 62 publications

References 114 publications

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease

Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease

Neuropathology of Dementia Disorders

Cerebral Multimorbidity in Aging

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