ANA TEREZA DI LORENZO ALHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis(2018) NASCIMENTO, C.; ALHO, A. T. Di Lorenzo; AMARAL, C. Bazan Conceicao; LEITE, R. E. P.; NITRINI, R.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; HOKKANEN, S. R. K.; HUNTER, S.; KEAGE, H.; KOVACS, G. G.; GRINBERG, L. T.; SUEMOTO, C. K.ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed.
- Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease(2017) EHRENBERG, A. J.; NGUY, A. K.; THEOFILAS, P.; DUNLOP, S.; SUEMOTO, C. K.; ALHO, A. T. Di Lorenzo; LEITE, R. P.; RODRIGUEZ, R. Diehl; MEJIA, M. B.; RUEB, U.; FARFEL, J. M.; FERRETTI-REBUSTINI, R. E. de Lucena; NASCIMENTO, C. F.; NITRINI, R.; PASQUALLUCCI, C. A.; JACOB-FILHO, W.; MILLER, B.; SEELEY, W. W.; HEINSEN, H.; GRINBERG, L. T.AimsHyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.MethodsWe utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-m-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases.ResultsIn Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9x between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN.ConclusionsLC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes.