Acta Neuropathologica Communications最新文献

{"title":"Correction: SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex.","authors":"Jennifer L Brown, Damyan W Hart, Gabriel E Boyle, Taylor G Brown, Michael LaCroix, Andrés M Baraibar, Ross Pelzel, Minwoo Kim, Mathew A Sherman, Samuel Boes, Michelle Sung, Tracy Cole, Michael K Lee, Alfonso Araque, Sylvain E Lesné","doi":"10.1186/s40478-024-01789-w","DOIUrl":"10.1186/s40478-024-01789-w","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"92"},"PeriodicalIF":7.1,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multiverse of α-synuclein: investigation of prion strain properties with carboxyl-terminal truncation specific antibodies in animal models.","authors":"Grace M Lloyd, Stephan Quintin, Zachary A Sorrentino, Kimberly-Marie M Gorion, Brach M Bell, Brooke Long, Giavanna Paterno, Benoit I Giasson","doi":"10.1186/s40478-024-01805-z","DOIUrl":"10.1186/s40478-024-01805-z","url":null,"abstract":"<p><p>Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of misfolded α-Synuclein (αSyn) in the brain. These conditions manifest with diverse clinical and pathophysiological characteristics. This disease diversity is hypothesized to be driven by αSyn strains with differing biophysical properties, potentially influencing prion-type propagation and consequentially the progression of illness. Previously, we investigated this hypothesis by injecting brain lysate (seeds) from deceased individuals with various synucleinopathies or human recombinant αSyn preformed fibrils (PFFs) into transgenic mice overexpressing either wild type or A53T human αSyn. In the studies herein, we expanded on these experiments, utilizing a panel of antibodies specific for the major carboxyl-terminally truncated forms of αSyn (αSynΔC). These modified forms of αSyn are found enriched in human disease brains to inform on potential strain-specific proteolytic patterns. With monoclonal antibodies specific for human αSyn cleaved at residues 103, 114, 122, 125, and 129, we demonstrate that multiple system atrophy (MSA) seeds and PFFs induce differing neuroanatomical spread of αSyn pathology associated with host specific profiles. Overall, αSyn cleaved at residue 103 was most widely present in the induced pathological inclusions. Furthermore, αSynΔC-positive inclusions were present in astrocytes, but more frequently in activated microglia, with patterns dependent on host and inoculum. These findings support the hypothesis that synucleinopathy heterogeneity might stem from αSyn strains with unique biochemical properties that include proteolytic processing, which could result in dominant strain properties.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"91"},"PeriodicalIF":6.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks.","authors":"Fanny Eysert, Paula-Fernanda Kinoshita, Julien Lagarde, Sandra Lacas-Gervais, Laura Xicota, Guillaume Dorothée, Michel Bottlaender, Frédéric Checler, Marie-Claude Potier, Marie Sarazin, Mounia Chami","doi":"10.1186/s40478-024-01807-x","DOIUrl":"10.1186/s40478-024-01807-x","url":null,"abstract":"<p><p>Mitochondrial dysfunctions are key features of Alzheimer's disease (AD). The occurrence of these disturbances in the peripheral cells of AD patients and their potential correlation with disease progression are underinvestigated. We studied mitochondrial structure, function and mitophagy in fibroblasts from healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, namely, (i) Mini-Mental State Examination (MMSE) and (ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB), and with (iii) amyloid beta (Aβ) plaque burden (PiB-PET imaging) and (iv) the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs). We revealed alterations in mitochondrial structure as well as specific mitochondrial dysfunction signatures in AD-MCI and AD-D fibroblasts and revealed that defective mitophagy and autophagy are linked to impaired lysosomal activity in AD-D fibroblasts. We reported significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation. This study emphasizes the potential use of peripheral cells for investigating AD pathophysiology.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"90"},"PeriodicalIF":6.2,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau modulation through AAV9 therapy augments Akt/Erk survival signalling in glaucoma mitigating the retinal degenerative phenotype.","authors":"Kanishka Pushpitha Maha Thananthirige, Nitin Chitranshi, Devaraj Basavarajappa, Rashi Rajput, Mojdeh Abbasi, Viswanthram Palanivel, Veer Bala Gupta, Joao A Paulo, Maya Koronyo-Hamaoui, Mehdi Mirzaei, Stuart L Graham, Vivek Gupta","doi":"10.1186/s40478-024-01804-0","DOIUrl":"10.1186/s40478-024-01804-0","url":null,"abstract":"<p><p>The microtubule-associated protein Tau is a key player in various neurodegenerative conditions, including Alzheimer's disease (AD) and Tauopathies, where its hyperphosphorylation disrupts neuronal microtubular lattice stability. Glaucoma, a neurodegenerative disorder affecting the retina, leads to irreversible vision loss by damaging retinal ganglion cells and the optic nerve, often associated with increased intraocular pressure. Prior studies have indicated Tau expression and phosphorylation alterations in the retina in both AD and glaucoma, yet the causative or downstream nature of Tau protein changes in these pathologies remains unclear. This study investigates the impact of Tau protein modulation on retinal neurons under normal and experimental glaucoma conditions. Employing AAV9-mediated gene therapy for Tau overexpression and knockdown, both manipulations were found to adversely affect retinal structural and functional measures as well as neuroprotective Akt/Erk survival signalling in healthy conditions. In the experimental glaucoma model, Tau overexpression intensified inner retinal degeneration, while Tau silencing provided significant protection against these degenerative changes. These findings underscore the critical role of endogenous Tau protein levels in preserving retinal integrity and emphasize the therapeutic potential of targeting Tau in glaucoma pathology.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"89"},"PeriodicalIF":6.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11158005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Torpor induces reversible tau hyperphosphorylation and accumulation in mice expressing human tau.","authors":"C F de Veij Mestdagh, M E Witte, W Scheper, A B Smit, R H Henning, R E van Kesteren","doi":"10.1186/s40478-024-01800-4","DOIUrl":"10.1186/s40478-024-01800-4","url":null,"abstract":"<p><p>Tau protein hyperphosphorylation and aggregation are key pathological events in neurodegenerative tauopathies such as Alzheimer's disease. Interestingly, seasonal hibernators show extensive tau hyperphosphorylation during torpor, i.e., the hypothermic and hypometabolic state of hibernation, which is completely reversed during arousal. Torpor-associated mechanisms that reverse tau hyperphosphorylation may be of therapeutic relevance, however, it is currently not known to what extent they apply to human tau. Here we addressed this issue using daily torpor in wildtype mice that express mouse tau (mtau) and in mice that lack mtau expression and instead express human tau (htau). AT8, AT100 and Ser396 immunoblotting and immunohistochemistry were used to assess tau (hyper)phosphorylation at clinically relevant phosphorylation sites. We found that torpor robustly and reversibly increases the levels of phosphorylated tau in both mtau and htau mice. Immunohistochemistry revealed four brain areas that show prominent tau phosphorylation: the hippocampus, posterior parietal cortex, piriform cortex and cortical amygdala. Whereas wildtype mice primarily showed increased levels of diffusely organized hyperphosphorylated tau during torpor, htau mice contained clear somato-dendritic accumulations of AT8 reactivity resembling tau pre-tangles as observed in the Alzheimer brain. Interestingly, AT8-positive accumulations disappeared upon arousal, and tau phosphorylation levels at 24 h after arousal were lower than observed at baseline, suggesting a beneficial effect of torpor-arousal cycles on preexisting hyperphosphorylated tau. In conclusion, daily torpor in mice offers a quick and standardized method to study tau phosphorylation, accumulation and clearance in mouse models relevant for neurodegeneration, as well as opportunities to discover new targets for the treatment of human tauopathies.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"86"},"PeriodicalIF":6.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Anatomic survey of seeding in Alzheimer's disease brains reveals unexpected patterns.","authors":"Barbara E Stopschinski, Kelly Del Tredici, Sandi-Jo Estill-Terpack, Estifanos Ghebremedhin, Fang F Yu, Heiko Braak, Marc I Diamond","doi":"10.1186/s40478-024-01795-y","DOIUrl":"10.1186/s40478-024-01795-y","url":null,"abstract":"","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"87"},"PeriodicalIF":7.1,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.","authors":"Bruce A Berkowitz, Anuhya Paruchuri, Josh Stanek, Mura Abdul-Nabi, Robert H Podolsky, Abner Heredia Bustos, Karen Lins Childers, Geoffrey G Murphy, Katherine Stangis, Robin Roberts","doi":"10.1186/s40478-024-01799-8","DOIUrl":"10.1186/s40478-024-01799-8","url":null,"abstract":"<p><p>Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied. The contrast sensitivity (CS), external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness (a proxy for low pH-triggered water removal), profile shape of the hyperreflective band just posterior to the ELM (i.e., the mitochondrial configuration within photoreceptors per aspect ratio [MCP/AR]), and retinal laminar thickness were measured. Both wild-type substrains showed similar visual performance indices and dark-evoked ELM-RPE contraction. The lack of a light-dark change in B6NTac MCP/AR, unlike in B6J mice, is consistent with relatively greater mitochondrial efficiency. 5xFAD B6J mice, but not 5xFAD B6NTac mice, showed lower-than-WT CS. Light-adapted 5xFAD substrains both showed abnormal ELM-RPE contraction and greater-than-WT MCP/AR contraction. The inner retina and superior outer retina were thinner. Treating 5xFAD B6J mice with R-carvedilol + DMSO or DMSO alone corrected CS and ELM-RPE contraction but not supernormal MCP/AR contraction or laminar thinning. These results provide biomarker evidence for prodromal photoreceptor mitochondrial dysfunction/oxidative stress/oxidative damage, which is unrelated to visual performance, as well as the presence of the Nnt gene. This pathophysiology is druggable in 5xFAD mice.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"85"},"PeriodicalIF":6.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human post-mortem organotypic brain slice cultures: a tool to study pathomechanisms and test therapies.","authors":"Bonnie C Plug, Ilma M Revers, Marjolein Breur, Gema Muñoz González, Jaap A Timmerman, Niels R C Meijns, Daniek Hamberg, Jikke Wagendorp, Erik Nutma, Nicole I Wolf, Antonio Luchicchi, Huibert D Mansvelder, Niek P van Til, Marjo S van der Knaap, Marianna Bugiani","doi":"10.1186/s40478-024-01784-1","DOIUrl":"10.1186/s40478-024-01784-1","url":null,"abstract":"<p><p>Human brain experimental models recapitulating age- and disease-related characteristics are lacking. There is urgent need for human-specific tools that model the complex molecular and cellular interplay between different cell types to assess underlying disease mechanisms and test therapies. Here we present an adapted ex vivo organotypic slice culture method using human post-mortem brain tissue cultured at an air-liquid interface to also study brain white matter. We assessed whether these human post-mortem brain slices recapitulate the in vivo neuropathology and if they are suitable for pathophysiological, experimental and pre-clinical treatment development purposes, specifically regarding leukodystrophies. Human post-mortem brain tissue and cerebrospinal fluid were obtained from control, psychiatric and leukodystrophy donors. Slices were cultured up to six weeks, in culture medium with or without human cerebrospinal fluid. Human post-mortem organotypic brain slice cultures remained viable for at least six weeks ex vivo and maintained tissue structure and diversity of (neural) cell types. Supplementation with cerebrospinal fluid could improve slice recovery. Patient-derived organotypic slice cultures recapitulated and maintained known in vivo neuropathology. The cultures also showed physiologic multicellular responses to lysolecithin-induced demyelination ex vivo, indicating their suitability to study intrinsic repair mechanisms upon injury. The slice cultures were applicable for various experimental studies, as multi-electrode neuronal recordings. Finally, the cultures showed successful cell-type dependent transduction with gene therapy vectors. These human post-mortem organotypic brain slice cultures represent an adapted ex vivo model suitable for multifaceted studies of brain disease mechanisms, boosting translation from human ex vivo to in vivo. This model also allows for assessing potential treatment options, including gene therapy applications. Human post-mortem brain slice cultures are thus a valuable tool in preclinical research to study the pathomechanisms of a wide variety of brain diseases in living human tissue.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"83"},"PeriodicalIF":6.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-synuclein aggregates are phosphatase resistant.","authors":"S G Choi, T Tittle, D Garcia-Prada, J H Kordower, R Melki, B A Killinger","doi":"10.1186/s40478-024-01785-0","DOIUrl":"10.1186/s40478-024-01785-0","url":null,"abstract":"<p><p>Alpha-synuclein (αsyn) is an intrinsically disordered protein that aggregates in the brain in several neurodegenerative diseases collectively called synucleinopathies. Phosphorylation of αsyn at serine 129 (PSER129) was considered rare in the healthy human brain but is enriched in pathological αsyn aggregates and is used as a specific marker for disease inclusions. However, recent observations challenge this assumption by demonstrating that PSER129 results from neuronal activity and can be readily detected in the non-diseased mammalian brain. Here, we investigated experimental conditions under which two distinct PSER129 pools, namely endogenous-PSER129 and aggregated-PSER129, could be detected and differentiated in the mammalian brain. Results showed that in the wild-type (WT) mouse brain, perfusion fixation conditions greatly influenced the detection of endogenous-PSER129, with endogenous-PSER129 being nearly undetectable after delayed perfusion fixation (30-min and 1-h postmortem interval). Exposure to anesthetics (e.g., Ketamine or xylazine) before perfusion did not significantly influence endogenous-PSER129 detection or levels. In situ, non-specific phosphatase calf alkaline phosphatase (CIAP) selectively dephosphorylated endogenous-PSER129 while αsyn preformed fibril (PFF)-seeded aggregates and genuine disease aggregates (Lewy pathology and Papp-Lantos bodies in Parkinson's disease and multiple systems atrophy brain, respectively) were resistant to CIAP-mediated dephosphorylation. The phosphatase resistance of aggregates was abolished by sample denaturation, and CIAP-resistant PSER129 was closely associated with proteinase K (PK)-resistant αsyn (i.e., a marker of aggregation). CIAP pretreatment allowed for highly specific detection of seeded αsyn aggregates in a mouse model that accumulates non-aggregated-PSER129. We conclude that αsyn aggregates are impervious to phosphatases, and CIAP pretreatment increases detection specificity for aggregated-PSER129, particularly in well-preserved biological samples (e.g., perfusion fixed or flash-frozen mammalian tissues) where there is a high probability of interference from endogenous-PSER129. Our findings have important implications for the mechanism of PSER129-accumulation in the synucleinopathy brain and provide a simple experimental method to differentiate endogenous-from aggregated PSER129.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"84"},"PeriodicalIF":6.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuropathological landscape of small vessel disease and Lewy pathology in a cohort of Hispanic and non-Hispanic White decedents with Alzheimer disease.","authors":"Hsin-Pei Wang, Rebeca Scalco, Naomi Saito, Laurel Beckett, My-Le Nguyen, Emily Z Huie, Lawrence S Honig, Charles DeCarli, Robert A Rissman, Andrew F Teich, Dan M Mungas, Lee-Way Jin, Brittany N Dugger","doi":"10.1186/s40478-024-01773-4","DOIUrl":"10.1186/s40478-024-01773-4","url":null,"abstract":"<p><p>Cerebrovascular and α-synuclein pathologies are frequently observed alongside Alzheimer disease (AD). The heterogeneity of AD necessitates comprehensive approaches to postmortem studies, including the representation of historically underrepresented ethnic groups. In this cohort study, we evaluated small vessel disease pathologies and α-synuclein deposits among Hispanic decedents (HD, n = 92) and non-Hispanic White decedents (NHWD, n = 184) from three Alzheimer's Disease Research Centers: Columbia University, University of California San Diego, and University of California Davis. The study included cases with a pathological diagnosis of Intermediate/High AD based on the National Institute on Aging- Alzheimer's Association (NIA-AA) and/or NIA-Reagan criteria. A 2:1 random comparison sample of NHWD was frequency-balanced and matched with HD by age and sex. An expert blinded to demographics and center origin evaluated arteriolosclerosis, cerebral amyloid angiopathy (CAA), and Lewy bodies/Lewy neurites (LBs/LNs) with a semi-quantitative approach using established criteria. There were many similarities and a few differences among groups. HD showed more severe Vonsattel grading of CAA in the cerebellum (p = 0.04), higher CAA density in the posterior hippocampus and cerebellum (ps = 0.01), and increased LBs/LNs density in the frontal (p = 0.01) and temporal cortices (p = 0.03), as determined by Wilcoxon's test. Ordinal logistic regression adjusting for age, sex, and center confirmed these findings except for LBs/LNs in the temporal cortex. Results indicate HD with AD exhibit greater CAA and α-synuclein burdens in select neuroanatomic regions when compared to age- and sex-matched NHWD with AD. These findings aid in the generalizability of concurrent arteriolosclerosis, CAA, and LBs/LNs topography and severity within the setting of pathologically confirmed AD, particularly in persons of Hispanic descent, showing many similarities and a few differences to those of NHW descent and providing insights into precision medicine approaches.</p>","PeriodicalId":6914,"journal":{"name":"Acta Neuropathologica Communications","volume":"12 1","pages":"81"},"PeriodicalIF":6.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}