Journals
2025 EN
Ngoubangoye Barthélémy · Dibakou SergeEly · Otsaghe Ekore Désiré
+6 more
ABSTRACT This study aimed to establish a baseline hematological profile and examine the influence of age, sex, and season on hematological parameters in captive chimpanzees ( Pan troglodytes ) living in a humid tropical climate. Hematological parameters are a useful tool for assessing health status and diagnosing diseases in animals. We analyzed 473 blood samples collected from 84 chimpanzees (43 females and 41 males) during annual health checks, conducted under anesthesia for a routine physical examination. The main findings revealed significant sex differences in some hematological parameters: males had higher hematocrit and red blood cell counts than females. Age‐related variations have also been noted, with adolescents and adults having lower lymphocyte counts but higher neutrophil and monocyte counts than infants. Adults, in particular, had significantly lower platelet counts compared to other age classes. Seasonal fluctuations were also observed: lymphocyte counts were higher in the rainy season, while neutrophil counts were higher in the dry season. In addition, the general trends in hematological parameters for this captive population of chimpanzees were similar to those reported in captive chimpanzees living in the United States. These results should provide animal health professionals, particularly those working with nonhuman primates, with data to compare and interpret. They will help improve practices for monitoring and managing the health of nonhuman primates in captivity.
Journals
2025 EN
Novoseltseva Anna · Kureli Gulce · Chang Shuaibin
+10 more
Abstract INTRODUCTION Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) are tauopathies with gray matter (GM) myelin changes that are challenging to assess with standard imaging. New methods are needed to quantify myelin integrity in autopsy brain tissues. METHODS We used polarization‐sensitive optical coherence tomography (PS‐OCT) to measure bulk tissue relative retardance and birefringence microscopy for high‐resolution imaging of myelin degradation. Samples included five AD, five CTE, and four age‐matched normal controls. RESULTS When controlling for age and postmortem interval, no statistically significant differences in white matter retardance or GM myelin defect density were observed between groups. The age difference between controls (64 ± 4.7 years, mean ± SD) and disease groups (80.3 ± 7 years) emerged as an important confounding factor. Amyloid beta and tau staining showed weak correlations with myelin defects. DISCUSSION Our label‐free approach enables large‐volume imaging of brain tissue, a valuable tool for studying myelin changes in neurodegenerative diseases. Highlights Multi‐modal assessment of myelin integrity using polarization‐sensitive optical coherence tomography (PS‐OCT) and high‐resolution birefringence microscopy. Age emerged as a critical confounding factor; no significant disease differences were found. Weak correlation between myelin defects and deposition of amyloid beta/tau was found in prefrontal gray matter. Label‐free optical methods enable high‐resolution, large‐volume imaging of myelin.
Journals
2025 EN
Paauw Dominique · Heger Irene · Horstkötter Dorothee
+2 more
Abstract INTRODUCTION To lower future dementia incidence, there is an urgent need to implement dementia risk reduction strategies in routine care. Yet, it remains unclear whether health professionals possess sufficient knowledge. METHODS A cross‐sectional survey was conducted among 368 current and 692 future (i.e., students) health professionals in the Netherlands, assessing awareness of dementia risk reduction, knowledge of dementia risk factors, and educational needs and barriers. RESULTS Most professionals (79.1%) and students (54.1%) were aware of dementia risk reduction. Across both groups, highly educated individuals demonstrated greater awareness and better recognition of risk factors. Knowledge gaps existed within both groups regarding the contribution of hearing impairment, obesity, poor sleep, and chronic kidney disease. Both groups expressed interest in professional education on brain health promotion. DISCUSSION These findings highlight the need for tailored educational modules to address knowledge gaps and equip professionals with the tools to discuss dementia risk reduction in routine care. Highlights Most professionals and students were aware of dementia risk reduction possibilities. Highly educated individuals demonstrated greater awareness and better recognition of dementia risk factors than those with lower education levels. Both professionals and students had knowledge gaps regarding specific dementia risk factors. Few students received comprehensive education on dementia risk reduction as part of their studies. The majority of professionals and students expressed interest in further (professional) education on improving brain health and dementia risk reduction.
Journals
2025 EN
Lorenz Linda M. C. · Rohde Susan K. · Luimes Maruelle C.
+11 more
Abstract INTRODUCTION Whether Alzheimer's disease (AD)‐associated plasma biomarkers reflect cognitive performance and neuropathology in the oldest old remains unclear. METHODS In plasma samples from 255 centenarians from the longitudinal 100‐plus Study (median age 101.2 years), we quantified biomarkers amyloid beta (Aβ)42/40 ratio, Aβ40, Aβ42, phosphorylated tau 181 (pTau‐181)/Aβ42 ratio, pTau‐181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations. These were associated with same‐day measures of cognitive performance and, for centenarians who donated their brain ( n = 60), with post mortem Aβ and tau neuropathology. RESULTS Cognition ranged from high to early cognitive decline (median Mini‐Mental State Examination [MMSE] score = 26). Lower plasma Aβ40 and Aβ42 are associated with poorer executive functioning, attention/processing speed, and higher Aβ neuropathology. Elevated plasma NfL and GFAP are associated with poorer executive functioning, slower processing speed, and Aβ and tau neuropathology. Higher plasma pTau‐181 and the pTau‐181/Aβ42 ratio are associated with Aβ and tau neuropathology, but not with cognitive performance. The Aβ42/40 ratio was uninformative. DISCUSSION Plasma Aβ, NfL, and GFAP detected neuropathology and early cognitive decline in centenarians; plasma pTau‐181 and the pTau‐181/Aβ42 ratio primarily report more advanced neuropathology. Highlights Lower plasma Aβ40 and Aβ42 concentrations are associated with poorer executive functioning and higher Aβ neuropathology, and thus may detect early cognitive decline in centenarians. Higher plasma pTau‐181 concentrations and the pTau‐181/Aβ42 ratio are strongly associated with Aβ and tau neuropathology; however, they are not associated with cognitive performance. Higher NfL concentrations are associated with higher Aβ and tau neuropathology. Higher plasma NfL and GFAP concentrations are associated with poorer attention and processing speed and may detect early cognitive decline in centenarians.
Journals
2025 EN
Rohde Susan K. · Luimes Maruelle C. · Rozemuller Annemieke J.M.
+9 more
Abstract Background The hippocampus is differentially affected in Alzheimer's disease neuropathologic change (ADNC) versus primary age‐related tauopathy (PART), an amyloid‐beta (Aβ)‐independent tauopathy: the CA2/CA1 hyperphosphorylated tau (pTau)‐ratio is higher in PART, which inversely correlates with Aβ‐burden. However, as the aging brain often presents mixed rather than uniform pathologies, we questioned whether these distinct hippocampal pTau distributions persist into extreme ages and how hippocampal Aβ‐ and pTau‐distributions correlate with cognition in centenarians. Method We quantified Aβ‐ (6F/3D) and pTau (AT8)‐burdens across eight hippocampal and parahippocampal subregions in 112 centenarians (median age 104, IQR 102‐105), alongside 11 AD (median age 84, IQR 72‐86) and 7 PART cases for comparison (median age 88, IQR 78‐92; Figure 1). We compared CA2/CA1‐pTau‐ratio in centenarians who met PART criteria (Thal phase ≤2, Braak stage I‐IV; n = 49) with centenarians who met ADNC criteria (intermediate/high according to NIA‐AA guidelines; Thal phase ≥3, Braak stage III‐VI; n = 50). Cognitive performance was assessed using 13 neuropsychological tests shortly before brain donation (median 10 months, IQR5‐14, n = 72). Robust linear regression models were used to associate subregional Aβ‐ and pTau‐burdens with cognitive performance, while adjusting for age, sex, and education. Result In line with previous findings, CA2/CA1‐pTau‐ratios were higher in younger PART cases compared to AD patients (median 3.0, IQR 2.1‐3.6, min‐max 1.6‐4.2 vs. median 1.2, IQR 0.9‐1.4, min‐max 0.8‐1.4; p <0.001). Surprisingly, CA2/CA1‐pTau‐ratios in centenarians with PART were comparable to centenarians with ADNC (median 1.3, IQR 1.1‐2.0, min‐max 0.3‐10.8 vs. median 1.2, IQR 1.0‐1.8, min‐max 0.2‐6.2; p = 0.684). Accordingly, CA2/CA1‐pTau‐ratio in centenarians was unrelated to Aβ‐burden, Thal phase or Braak stage. Higher Aβ‐ and pTau‐burdens associated with lower cognition, though through different subregions: cognition associated with Aβ‐burden in the hippocampus (CA4, CA3, CA2, CA1/subiculum), whereas pTau‐burden in the parahippocampus (presubiculum, entorhinal cortex, fusiform gyrus) associated with cognition. Conclusion In the oldest‐old, PART and ADNC are less distinguishable by determinants observed in younger individuals: centenarians with ADNC may show age‐related Aβ accumulation alongside PART‐like pTau patterns, while centenarians meeting PART criteria do not always show PART‐like pTau patterns. However, hippocampal Aβ‐burden and parahippocampal pTau‐burden associate with cognitive decline, highlighting subregional‐specific vulnerability to pathology‐driven cognitive decline.
Journals
2025 EN
Leitner Dominique · Kanshin Evgeny · Balcomb Kaleah
+7 more
Abstract Background Amyloid plaques contain numerous proteins in addition to amyloid beta. Previous unbiased comprehensive localized proteomics identified plaque associated proteins in late‐onset AD (LOAD), early‐onset AD (EOAD), rapidly progressive AD (rpAD), AD in Down syndrome (DS), and preclinical AD, although with some studies having smaller cohorts and more focus on severe pathology. The amyloid plaque protein differences in mild cognitive impairment (MCI) have not been evaluated, nor how these protein differences compare to a larger AD cohort. Method We evaluated the plaque proteomes in MCI and AD with comparisons to neighboring non‐plaque tissue and control non‐plaque tissue from ROSMAP (153 cases ( n = 244 samples); control ( n = 62), MCI ( n = 36), AD ( n = 55)). Tissue was microdissected from autopsy paraffin embedded temporal cortex and evaluated by label‐free quantitative mass spectrometry. Protein differences and complementary histology characterization of top proteins were evaluated. Result We identified a number of differentially abundant proteins in MCI and AD plaque tissue compared to neighboring non‐plaque tissue (false discovery rate, FDR<5%). These included proteins described previously as well as novel proteins. The gene ontology (GO) terms associated with these proteins included increased inflammatory response in both MCI and AD, as well as decreased myelin in AD. Of proteins altered in at least one disease group, there were a number of proteins that were shared in MCI and AD plaque tissue vs neighboring non‐plaque. In non‐plaque tissue, increased proteins were related to GO terms DNA recombination and decreased proteins with actin‐myosin filament in AD; and there were some shared altered proteins in MCI and AD but had a mild positive correlation. Weighted gene correlation network analysis (WGCNA) evaluated how protein levels corresponded to case history and identified a number of associated proteins with regional pathology levels, overall pathology, and demographics,. After comparative analyses with other brain tissue and biofluid proteomic datasets, top protein candidates were identified and characterized further by histology. Conclusion We have conducted the most extensive proteomic analysis of microdissected plaque proteomes in MCI and AD, with correlations to case history. Our results provide valuable insights into molecular mechanisms, novel diagnostic biomarkers, and potential therapeutic strategies.
Journals
2025 EN
Li Chenyang · Leitner Dominique · Pang Huize
+6 more
Abstract Background White matter hyperintensities (WMHs), visible as increased signal intensity on T2‐FLAIR MRI images, represents a key imaging biomarker in the Alzheimer's Disease and related dementias (AD/ADRD). Histopathology links WMHs to demyelination, axonal degeneration and loss, reactive astrogliosis and microglial activation. However, direct quantitative correlations between in vivo MRI signals and specific histopathological features are challenging due to differences in spatial resolution and the indirect nature of MRI. This study aims to bridge clinical MRI findings of WMHs with histopathological findings using multiparametric and multiscale MRI approaches in dementia brains. Method Two post‐mortem brain specimens from pathologically confirmed AD cases were included in this study. The imaging protocol includes sequential MRI acquisitions at 3T. Whole‐hemispheric imaging was initially performed using a 3T clinical system. The specimens were then sectioned into tissue blocks sized to fit histological cassettes. For high‐resolution ex vivo imaging, each tissue block was imaged on a preclinical 3T MRI system, using the same imaging protocols as the hemispheric scans but with improved resolution. Result Postmortem hemisphere scans on a clinical scanner demonstrated that WMHs showed comparable contrast to in vivo imaging. Quantitative analysis of multimodal imaging data of WMHs from both preclinical and clinical 3T scanners, exhibited increased mean diffusivity (MD) and prolonged T1, T2, and T2* relaxation times compared to surrounding normal appearing white matter (NAWM). Histopathological staining confirmed spatial overlap between tissue block MRI and histological findings of WMHs, highlighting pathological features of white mater vacuolation, demyelination, astrogliosis and neuroinflammation. Conclusion In conclusion, the joint analysis of high‐resolution postmortem MRI and histopathology revealed a complex signal origin of WMHs, characterized by elevated diffusivity and prolonged T1 and T2 relaxation times, which correlate with various histological findings. This preliminary study may provide insights into the signal composition of WMHs in vivo . Figure 1 . Representative half hemisphere MRI data used to evaluate WMHs. Figure 2 . High‐resolution MRI of small tissue cassettes at 3T and (B) Histology of WMHs using LFB, MBP, GFAP, and IBA1 staining of WMHs. Figure 3 . Spider plot of the multiparametric measurements between ( A ) NAWM and ( B ) WMHs from a single subject.
Journals
2025 EN
Li Chenyang · Pang Huize · Li Annie
+6 more
Abstract Background To interpret clinical Alzheimer's disease (AD) pathology, postmortem MRI is frequently used to provide crucial insights into brain structure and vasculature, bridging in vivo imaging and histopathological validation. However, imaging blood and vascular changes after death and fixation remains poorly understood. Traditional vascular contrast agents are ineffective in postmortem imaging studies due to lack of circulation, posing challenges for vascular mapping of postmortem tissues. This study is to explore how blood clots can be used as contrast media to enhance postmortem vascular MRI. Method We studied three human brain tissues with postmortem diagnosis of epilepsy, Parkinson's Disease and AD, acquired from the NYU ADRC. The brain hemisphere was scanned first using human whole‐body 7T scanner. This is followed by cutting the hemisphere into smaller tissue chunks, including the prefrontal cortex and hippocampus, for high resolution preclinical MRI on animal scanners. Subsequently, histopathological staining, using hematoxylin and eosin (H&E) and Luxol fast blue stains (LFB), were performed to evaluate the vascular morphology and blood clot formation. Result High resolution susceptibility weighted imaging (SWI) of post‐mortem brain revealed clear small vessel contrast in grey matter and white matter, comparable to in vivo USPIO‐enhanced 7T MRI (Figure 1A and C). Moreover, intrahippocampal vasculatures were well illustrated in postmortem MRI, closely resembling USPIO‐enhanced clinical MRI findings (Figure 2E‐FC). Histopathology staining (HE and LFB staining) of hippocampal tissue demonstrated the blood clot vascular structures in the white matter, hippocampus and cortical regions (red arrow in Figure 3). Conclusion This study demonstrates the use of postmortem coagulated blood as an intrinsic contrast agent on T2*‐weighted images for visualizing small vasculatures, establishing a method for detailed vascular mapping in postmortem specimens alongside histopathological analysis. This approach can help to enhance our understanding of in vivo vascular imaging findings of vascular contributions to AD and AD‐related dementia and their underlying pathological substrates. Figure 1 . Comparison of high‐resolution T2*‐weighted data between postmortem and in vivo MRI . Figure 2 . Multi‐contrast MRI of post‐mortem hippocampus compared with histopathology and in vivo vascular MRI. Figure 3 . Blood clot formation (arrows) in postmortem brain tissue on T2*‐weighted imaging and histological staining.
Journals
2025 EN
Leitner Dominique · Li Chenyang · Pang Huize
+9 more
Abstract Background The choroid plexus (ChP), a highly vascularized structure within the ventricles, plays a vital role in cerebrospinal fluid (CSF) production and metabolic waste clearance, essential for brain homeostasis and function. In vivo imaging studies have identified age‐ and Alzheimer's disease (AD)‐related ChP changes, including increased size, vascular degeneration, and cyst‐like formations. We previously identified proteomic differences in severe AD cases compared to controls, associated with a shift in cell energy metabolism. However, investigation of underlying mechanisms remains limited. We sought to characterize ChP alterations in AD using histopathology and proteomics, focusing on blood‐CSF barrier integrity, vascular membrane changes, Aβ and tau accumulation, and epithelial and stromal tissue alterations. Method We evaluated the ChP by MRI, neuropathology, and proteomic analyses in AD and control cases. MRI findings were compared to our prior study on ChP using the HCP‐aging dataset (PMID: 39639335). Neuropathology characterization included Aβ, tau, endothelial marker CD31, epithelial marker AQP1, basement marker collagen IV (COL4). To follow up on our previous proteomic studies and identify protein changes across the AD continuum, we evaluated microdissected ChP from autopsy paraffin embedded tissue adjacent to the hippocampus at the level of the lateral geniculate nucleus, followed by label‐free quantitative mass spectrometry. Protein differences and complementary histology characterization and quantification of top proteins were evaluated, with correlations to case history. Result Proteomics identified protein differences across the AD continuum, with some proteins previously described as well as novel proteins. Functional associations with altered proteins were evaluated by gene ontology (GO) enrichment. After comparative analyses with other brain tissue and biofluid proteomic datasets, top protein candidates were identified and characterized by histology. Conclusion We performed an initial characterization of the ChP by MRI and neuropathology, and identified proteomic differences in AD. Our results provide valuable insights into molecular mechanisms, novel diagnostic biomarkers, and potential therapeutic strategies.
Journals
2025 EN
Ariza Mitchell Marta · Leitner Dominique · Kanshin Evgeny
+6 more
Abstract Background Down syndrome (DS) is the most common genetic form of Alzheimer's disease (AD) and is characterized by early amyloid‐β (Aβ) and phosphorylated tau (pTau) deposition, related to APP triplication. Our previous proteomics study comparing the Aβ plaque proteome in DS, early‐onset AD (EOAD), and late‐onset AD (LOAD) revealed multiple differentially abundant proteins linked to endo/lysosomal pathways, immune responses, and myelin function. While many of these proteins have been described in previous proteomics studies, several remain understudied in AD and DS, including some not previously reported in human AD proteomics. This study aims to characterize a selection of these proteins using immunohistochemistry to understand their roles in disease mechanisms, identify potential biomarkers, and explore novel therapeutic targets. Method Immunohistochemistry (IHC) was performed on sections from the temporal and frontal cortex of DS, EOAD, LOAD, and age‐matched control cases. Proteins of interest were selected based on their abundance in Aβ plaques and surrounding non‐plaque tissue, limited characterization in AD and DS, and potential roles in AD neuropathology. Result We selected the top altered proteins identified in Aβ plaques from our proteomics study for further characterization in DS, EOAD, and LOAD brain tissues. Our current work is the first to provide immunohistological evidence of these less‐studied proteins in the context of DS and AD. These proteins are associated with endo/lysosomal functions, synaptic activity, and myelin, and are linked to lysosomal storage diseases, protein aggregation, and the stability and maintenance of myelin sheaths. Conclusion Our findings reveal key functional characteristics of the amyloid plaque proteome in DS, compared to EOAD and LOAD, and enhance our understanding of underexplored proteins that play pivotal roles in AD neuropathology beyond Aβ and Tau pathologies. These results could pave the way for follow up mechanistic studies, novel diagnostic biomarkers, and therapeutic strategies in both DS and AD by shedding light on previously understudied proteins.