Biology subjects

Ortega-Cruz, D.

Publications and source records attributed to Ortega-Cruz, D..

3 recordsLinked to original sources

bioRxiv2023

Three-dimensional histology reveals dissociable human hippocampal long axis gradients of Alzheimer's pathology

INTRODUCTIONThree-dimensional (3D) histology analyses are essential to overcome sampling variability and understand pathological differences beyond the dissection axis. We present Path2MR, the first pipeline allowing 3D reconstruction of sparse human histology without an MRI reference. We implemented Path2MR with post-mortem hippocampal sections to explore pathology gradients in Alzheimers Disease. METHODSBlockface photographs of brain hemisphere slices are used for 3D reconstruction, from which an MRI-like image is generated using machine learning. Histology sections are aligned to the reconstructed hemisphere and subsequently to an atlas in standard space. RESULTSPath2MR successfully registered histological sections to their anatomical position along the hippocampal longitudinal axis. Combined with histopathology quantification, we found an expected peak of tau pathology at the anterior end of the hippocampus, while amyloid-{beta} displayed a quadratic anterior-posterior distribution. CONCLUSIONPath2MR, which enables 3D histology using any brain bank dataset, revealed significant differences along the hippocampus between tau and amyloid-{beta}.

neuroscience↗

bioRxiv2023

Hippocampal sclerosis of aging at post-mortem is evident on MRI more than a decade prior

INTRODUCTIONHippocampal sclerosis of aging (HS) is an important component of combined dementia neuropathology. However, the temporal evolution of its histologically-defined features is unknown. We investigated pre-mortem longitudinal hippocampal atrophy associated with HS, as well as with other dementia-associated pathologies. METHODSWe analyzed hippocampal volumes from MRI segmentations in 64 dementia patients with longitudinal MRI follow-up and post-mortem neuropathological evaluation, including HS assessment in the hippocampal head and body. RESULTSSignificant HS-associated hippocampal volume changes were observed thoughout the evaluated timespan, up to 11.75 years before death. These changes were independent of age and Alzheimers Disease (AD) burden, and specifically driven by CA1 and subiculum. AD burden, but not HS, significantly associated with the rate of hippocampal atrophy. DISCUSSIONHS-associated volume changes are detectable on MRI earlier than 10 years before death. These findings could contribute to the derivation of volumetric cut-offs for in vivo differentiation between HS and AD.

neuroscience↗

bioRxiv2022

A novel histological staging of hippocampal sclerosis that is evident in grey matter loss in vivo.

INTRODUCTIONHippocampal sclerosis of aging (HS) is defined by end-stage histological findings, strongly associated with limbic-predominant age-related TDP-43 encephalopathy (LATE). We aimed to characterize features of early HS to refine the understanding of its role within combined pathology. METHODSWe studied 159 brain donations from the multimodal Vallecas Alzheimers Center Study. A staging system (0 to IV) was developed to account for HS progression and analyzed in relation to pre-mortem cognitive and MRI data. RESULTSOur HS staging system displayed a significant correlation with disease duration, cognitive performance and combined neuropathologies, especially with LATE. Two-level assessment along the hippocampal longitudinal axis revealed an anterior-posterior gradient of HS severity. In vivo MRI showed focally reduced hippocampal grey matter density as a function of HS staging. DISCUSSIONThe association of this staging system with clinical progression and structural differences supports its utility in the characterization and potential in vivo monitoring of HS.

neuroscience↗