ANA TEREZA DI LORENZO ALHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
3 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.
- High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy(2018) ALHO, Eduardo Joaquim Lopes; ALHO, Ana Tereza Di Lorenzo; GRINBERG, Lea; AMARO JR., Edson; SANTOS, Glaucia Aparecida Bento dos; SILVA, Rafael Emidio da; NEVES, Ricardo Caires; ALEGRO, Maryana; COELHO, Daniel Boari; TEIXEIRA, Manoel Jacobsen; FONOFF, Erich Talamoni; HEINSEN, HelmutStereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.
- Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans(2018) THEOFILAS, Panos; EHRENBERG, Alexander J.; NGUY, Austin; THACKREY, Julia M.; DUNLOP, Sara; MEJIA, Maria B.; ALHO, Ana T.; LEITE, Renata Elaine Paraizo; RODRIGUEZ, Roberta Diehl; SUEMOTO, Cclaudia K.; NASCIMENTO, Camila F.; CHIN, Marcus; MEDINA-CLEGHORN, Daniel; CUERVO, Ana Maria; ARKIN, Michelle; SEELEY, William W.; MILLER, Bruce L.; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; JACOB FILHO, Wilson; RUEB, Udo; NEUHAUS, John; HEINSEN, Helmut; GRINBERG, Lea T.Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors. In progressive Braak stages, intraneuronal active caspase-6 positivity increases both alone and overlapping with NETs. Likewise, the proportion of NFT-bearing neurons showing autophagosomes increases. Overall, caspases may be involved in upstream cascades in AD and are associated with higher NFTs. Macroautophagy changes correlate with increasing NFT burden from early AD stages.