Biology subjects

Koronyo-Hamaoui, M.

Publications and source records attributed to Koronyo-Hamaoui, M..

3 recordsLinked to original sources

bioRxiv2024

Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance

IntroductionThe vascular contribution to Alzheimers disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. MethodsUsing scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures. ResultsPeri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count. DiscussionOur topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD. HighlightsO_LIRetinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions. C_LIO_LISecondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes. C_LIO_LICognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes. C_LI

pathology↗

bioRxiv2024

Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status

ImportanceThis study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimers disease (AD) and determines their relationship with disease status. ObjectiveA case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated tau (p-tau), and citrullinated tau (Cit-tau) in relation to the respective brain pathology and cognitive dysfunction in mild cognitively impaired (MCI) and AD dementia patients versus normal cognition (NC) controls. Design, setting and participantsEyes and brains from donors diagnosed with AD, MCI (due to AD), and NC were collected (n=75 in total), along with clinical and neuropathological data. Brain and retinal cross-sections-in predefined superior-temporal and inferior-temporal (ST/IT) subregions-were subjected to histopathology analysis or Nanostring GeoMx digital spatial profiling. Main outcomes and measureRetinal burden of NFTs (pretangles and mature tangles), PHF-tau, p-tau, oligo-tau, and Cit-tau was assessed in MCI and AD versus NC retinas. Pairwise correlations revealed associations between retinal and brain parameters and cognitive status. ResultsIncreased retinal NFTs (1.8-fold, p=0.0494), PHF-tau (2.3-fold, p<0.0001), oligo-tau (9.1-fold, p<0.0001), CitR209-tau (4.3-fold, p<0.0001), pSer202/Thr205-tau (AT8; 4.1-fold, p<0.0001), and pSer396-tau (2.8-fold, p=0.0015) were detected in AD patients. Retinas from MCI patients showed significant increases in NFTs (2.0-fold, p=0.0444), CitR209-tau (3.5-fold, p=0.0201), pSer396-tau (2.6-fold, p=0.0409), and, moreover, oligo-tau (5.8-fold, p=0.0045). Nanostring GeoMx quantification demonstrated upregulated retinal p-tau levels in MCI patients at phosphorylation sites of Ser214 (2.3-fold, p=0.0060), Ser396 (1.8-fold, p=0.0052), Ser404 (2.4-fold, p=0.0018), and Thr231 (3.3-fold, p=0.0028). Strong correlations were found between retinal tau forms to paired-brain pathology and cognitive status: a) retinal oligo-tau vs. Braak stage (r=0.60, P=0.0002), b) retinal PHF-tau vs. ABC average score (r=0.64, P=0.0043), c) retinal pSer396-tau vs. brain NFTs (r=0.68, P<0.0001), and d) retinal pSer202/Thr205-tau vs. MMSE scores (r= -0.77, P=0.0089). Conclusions and RelevanceThis study reveals increases in immature and mature retinal tau isoforms in MCI and AD patients, highlighting their relationship with brain pathology and cognition. The data provide strong incentive to further explore retinal tauopathy markers that may be useful for early detection and monitoring of AD staging through noninvasive retinal imaging.

pathology↗

bioRxiv2022

Label-Free Hyperspectral Imaging and Deep-Learning Prediction of Retinal Amyloid β-Protein and Phosphorylated Tau

Alzheimers disease (AD) is a major risk for the aging population. The pathological hallmarks of AD--an abnormal deposition of amyloid {beta}-protein (A{beta}) and phosphorylated tau (pTau)--have been demonstrated in the retinas of AD patients, including in prodromal patients with mild cognitive impairment (MCI). A{beta} pathology, especially the accumulation of the amyloidogenic 42-residue long alloform (A{beta}42), is considered an early and specific sign of AD, and together with tauopathy, confirms AD diagnosis. To visualize retinal A{beta} and pTau, state-of-the-art methods use fluorescence. However, administering contrast agents complicates the imaging procedure. To address this problem, we developed a label-free hyperspectral imaging method to detect the spectral signatures of A{beta}42 and pS396-Tau and predicted their abundance in retinal cross sections. For the first time, we reported the spectral signature of pTau and demonstrated an accurate prediction of A{beta} and pTau distribution powered by deep learning. We expect our finding will lay the groundwork for label-free detection of AD at its very earliest roots. Significance StatementThe pathological hallmarks of Alzheimers disease (AD), amyloid {beta}-protein (A{beta}) and hyperphosphorylated (p)Tau protein have been characterized by a hyperspectral camera in terms of spectral signatures. The unique optical properties of the hallmark proteins on the broad visible light range enable label-free and high-resolution detection and virtual staining of abnormal deposition in the retina tissue, which will lay the groundwork for AD early diagnosis and AD development quantification.

bioengineering↗