Neuropathological assessment of the Alzheimer spectrum

Jellinger, K. A.

doi:10.1007/s00702-020-02232-9

Cited by 47 publications

(23 citation statements)

References 265 publications

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“…163 Clinicopathological studies are therefore critical in shaping our understanding of the etiology, natural history, and mechanisms of disease and to help in formulating the frameworks necessary for the discovery of new therapeutic and preventative interventions. 123 In Africa, a post mortem study of brain tissue of neurologically normal Nigerian Africans showed incidental Lewy body pathology burden similar to figures that were then reported among individuals of European ancestry from the UK and United States. 164 The significance of this finding was the suggestion that the correspondence of the frequency 169 Similarly, a recent multiracial Brazilian neuropathological study showed a comparable reduction in AD pathology but higher vascular pathology in the brains of subjects of African ancestry.…”

Section: Insights From Neuropathologic Evaluationsupporting

confidence: 53%

“…111 Other dementia phenotypes reported in Africa include FTD; 112 dementia with Lewy bodies (DLB); 113 Parkinson's disease dementia (PDD); 71 and cognitive impairment or dementia associated with Creutzfeldt-Jakob disease, 114 Huntington disease, 115,116 and sickle cell disease (SCD). [117][118][119][120][121] However, confirmation of dementia subtypes is only definitive after post mortem neuropathologic examination and this level of diagnostic certainty has not been achieved in existing studies from Africa 122,123 with the exception of the first reported case of DLB. 113 SCD is well known to predispose to vascular brain injury, particularly silent cerebral infarction (SCI), which is often associated with cognitive impairment.…”

Section: Dementia Subtypes In Africamentioning

confidence: 99%

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Dementia in Africa: Current evidence, knowledge gaps, and future directions

Akinyemi

Yaria

Ojagbemi

et al. 2021

Alzheimer's & Dementia

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In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes.Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.

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Section: Insights From Neuropathologic Evaluationsupporting

confidence: 53%

Section: Dementia Subtypes In Africamentioning

confidence: 99%

Dementia in Africa: Current evidence, knowledge gaps, and future directions

Akinyemi

Yaria

Ojagbemi

et al. 2021

Alzheimer's & Dementia

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“…and pathological studies, and directed to the hallmark lesions of amyloid plaques and tau pathology [102,104,134,135]. Treatments targeting Aβ are still being evaluated with largely negative results to date [136][137][138][139].…”

Section: Accepted Articlementioning

confidence: 99%

Disease‐specific interactome alterations via epichaperomics: the case for Alzheimer’s disease

et al. 2021

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The increasingly appreciated prevalence of complicated stressor-to-phenotype associations in human disease requires a greater understanding of how specific stressors affect systems or interactome properties. Many currently untreatable diseases arise due to variations in, and through a combination of, multiple stressors of genetic, epigenetic, and environmental nature.Unfortunately, how such stressors lead to a specific disease phenotype or inflict a vulnerability to some cells and tissues but not others, remains largely unknown and unsatisfactorily addressed.Analysis of cell-and tissue-specific interactome networks may shed light on organization of biological systems and subsequently to disease vulnerabilities. However, deriving human interactomes across different cell-and disease-contexts remains a challenge. To this end, this opinion article links stressor-induced protein interactome network perturbations to the formation of pathologic scaffolds termed epichaperomes, revealing a viable and reproducible experimental solution to obtaining rigorous context-dependent interactomes. This article presents our views on how a specialized 'omics platform called epichaperomics may complement and enhance the currently available conventional approaches and aid the scientific community in defining, understanding, and ultimately controlling interactome networks of complex diseases such as Alzheimer's disease. Ultimately, this approach may aid the transition from a limited single-alteration perspective in disease to a comprehensive network-based mindset, which we posit will result in precision medicine paradigms for disease diagnosis and treatment.

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“…Since one of the pillars of 'precision medicine' is supported by biomarker-derived medical data, further improvements in the acquisition, integration, interpretation, and bioinformatics aspects of clinical data and the coordination and analysis of clinical, laboratory, molecular-genetic, and neuroimaging data, geriatric and psychological information and related healthcare resources should obtain significantly increased accuracy in the diagnostic synopsis for the "prospective AD patient". The significant heterogeneity of the AD condition: (i) will certainly benefit from an equally wide variety of AD biomarker-derived 'precision medicine'-oriented treatment approaches and/or data-driven pharmacological strategies; and (ii) whose biomarker-based therapeutic design will greatly improve the current situation regarding the healthcare, more effective and successful treatment, and the development of disease-modifying drugs for AD patients at any stage of the disease [10,22,65,68,71].…”

Section: Using Precision Medicine In the Diagnosis Of Admentioning

confidence: 99%

Biomarkers for Alzheimer’s Disease (AD) and the Application of Precision Medicine

Lukiw

Vergallo

Lista

et al. 2020

JPM

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An accurate diagnosis of Alzheimer’s disease (AD) currently stands as one of the most difficult and challenging in all of clinical neurology. AD is typically diagnosed using an integrated knowledge and assessment of multiple biomarkers and interrelated factors. These include the patient’s age, gender and lifestyle, medical and genetic history (both clinical- and family-derived), cognitive, physical, behavioral and geriatric assessment, laboratory examination of multiple AD patient biofluids, especially within the systemic circulation (blood serum) and cerebrospinal fluid (CSF), multiple neuroimaging-modalities of the brain’s limbic system and/or retina, followed up in many cases by post-mortem neuropathological examination to finally corroborate the diagnosis. More often than not, prospective AD cases are accompanied by other progressive, age-related dementing neuropathologies including, predominantly, a neurovascular and/or cardiovascular component, multiple-infarct dementia (MID), frontotemporal dementia (FTD) and/or strokes or ‘mini-strokes’ often integrated with other age-related neurological and non-neurological disorders including cardiovascular disease and cancer. Especially over the last 40 years, enormous research efforts have been undertaken to discover, characterize, and quantify more effectual and reliable biological markers for AD, especially during the pre-clinical or prodromal stages of AD so that pre-emptive therapeutic treatment strategies may be initiated. While a wealth of genetic, neurobiological, neurochemical, neuropathological, neuroimaging and other diagnostic information obtainable for a single AD patient can be immense: (i) it is currently challenging to integrate and formulate a definitive diagnosis for AD from this multifaceted and multidimensional information; and (ii) these data are unfortunately not directly comparable with the etiopathological patterns of other AD patients even when carefully matched for age, gender, familial genetics, and drug history. Four decades of AD research have repeatedly indicated that diagnostic profiles for AD are reflective of an extremely heterogeneous neurological disorder. This commentary will illuminate the heterogeneity of biomarkers for AD, comment on emerging investigative approaches and discuss why ‘precision medicine’ is emerging as our best paradigm yet for the most accurate and definitive prediction, diagnosis, and prognosis of this insidious and lethal brain disorder.

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Neuropathological assessment of the Alzheimer spectrum

Cited by 47 publications

References 265 publications

Dementia in Africa: Current evidence, knowledge gaps, and future directions

Dementia in Africa: Current evidence, knowledge gaps, and future directions

Disease‐specific interactome alterations via epichaperomics: the case for Alzheimer’s disease

Biomarkers for Alzheimer’s Disease (AD) and the Application of Precision Medicine

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