https://repositorio.fleni.org.ar/xmlui/handle/123456789/27 Thu, 10 Sep 2026 18:00:45 GMT 2026-09-10T18:00:45Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1577 Plasma levels of an N-terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease Schultz, Stephanie A.; Rao, Rao; Liu, Lei; Ostaszewski, Beth; Anderson, Amirah K.; Yau, Wai-Ying Wendy; Shirzadi, Zahra; Gordon, Brian A.; Hassenstab, Jason; Morris, John C.; Perrin, Richard J.; Allegri, Ricardo Francisco; Barthélemy, Nicolas R.; Fox, Nick C.; Day, Gregory S.; Jucker, Mathias; Levey, Allan I.; Levin, Johannes; Mori, Hiroshi; Salloway, Stephen Introduction: Tau species lacking truncation of the N-terminal region, including plasma N-terminal tau fragment 1 (NT1), have been previously associated with cognitive decline, neurodegeneration, and tau pathology in late-onset sporadic Alzheimer's disease (AD). Methods: Here, we examined cross-sectional and longitudinal plasma NT1 as a possible predictor of cognitive, clinical, and core AD biomarker trajectories in autosomal dominant AD (ADAD). Results: NT1 levels in ADAD mutation carriers (MC; n = 132) increased across the disease continuum, compared to non-carriers (NC; n = 75), becoming elevated about a decade prior to estimated symptom onset. Cross-sectional and longitudinal NT1 levels in MC were associated with clinical, cognitive, and biomarker changes. NT1 increases continued in symptomatic phases of disease, a distinct trajectory from that seen with CSF p-tau217 and other phospho-tau species. Discussion: Together, our results suggest that plasma NT1-alone or combined with other tau measures-may be useful in studying AD-related clinical, cognitive, and biomarker outcomes. Highlights: Leveraging a deeply phenotyped cohort of individuals carrying a pathogenic variant for autosomal dominant Alzheimer's disease (ADAD) and their non-carrier family members, our results suggest that plasma N-terminal tau fragment 1 (NT1) levels mirrored changes in clinical, cognitive, and neurodegenerative measures in ADAD, particularly in late asymptomatic and early symptomatic phases of disease. NT1 levels correlated with cerebrospinal fluid (CSF) measures of tau pathology but less so with CSF or imaging measures of β-amyloid pathology. Together with previous supportive findings in preclinical and symptomatic sporadic AD, these results suggest that plasma NT1-alone or combined with other tau measures-may be useful in studying AD-related tau pathology and neurodegeneration across a wide spectrum of disease. Mon, 01 Jun 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1577 2026-06-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1573 Recognition memory in individuals with mild cognitive impairment and Alzheimer's dementia : a systematic review Russo, María Julieta; Bueri, José; Ferrara, Lucía Alba; Labos, Edith; Sevlever, Gustavo Emilio; Allegri, Ricardo Francisco Background: Episodic memory impairment is a hallmark of Alzheimer's disease (AD) and is already present in its prodromal stage. While recall deficits are well established as predictors of memory performance, the role of recognition memory-particularly the dissociation between familiarity and recollection-remains less explored. Objective: This systematic review aims to synthesize current evidence on recognition memory performance in healthy controls (HC), individuals with mild cognitive impairment (MCI), and those with AD, with a focus on the distinct contributions of familiarity and recollection processes. Methods: We searched PubMed (MEDLINE), Science Direct, PubPsych, and TRIP Medical databases for studies published until November 2025, which investigated recognition memory performance in individuals with MCI and AD including validated memory tools (such as scales, indices, scores, tests, and assessments). Forty-six studies (n = 3996) met the criteria and were included. Methodological quality was evaluated using the Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42022343750. Results: Most studies were cross-sectional and conducted in memory clinics or research centers, with considerable heterogeneity in sample size and assessment tools. The majority utilized experimental paradigms to differentiate familiarity and recollection, though traditional memory tests remain prevalent. Across studies, recollection was consistently impaired in MCI and AD, while familiarity showed a more variable pattern-often preserved in early MCI but impaired in advanced stages and AD. Structural and functional neuroimaging studies revealed that hippocampal atrophy is closely linked to recollection deficits, while alterations in entorhinal and parahippocampal cortices are associated with familiarity impairment. Combined deficits in recall and recognition, especially when recognition impairment reflects encoding failure, robustly predict conversion to dementia. Conclusions: Recognition memory assessment, particularly the dissociation between familiarity and recollection, provides valuable information for early detection and prognosis in the AD continuum. Incorporating nuanced recognition memory measures into clinical practice may improve diagnostic specificity and facilitate timely interventions. Further longitudinal research is needed to validate recognition memory as a predictor of dementia progression and to standardize its assessment in diverse populations. Tue, 06 Jan 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1573 2026-01-06T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1561 Paramagnetic Rim Lesions and Development of Clinical MS in Radiologically Isolated Syndrome Lim, Timothy Reynold; Suthiphosuwan, Suradech; Gaitán, María Inés; Marrodán, Mariano; Horwath, Elizabeth A.; Guenette, Melanie; Bharatha, Aditya; Sati, Pascal; Absinta, Martina; Correale, Jorge; Shinohara, Russell; Reich, Daniel S.; Oh, Jiwon Importance: Most people with radiologically isolated syndrome (RIS) have high proportions of white matter lesions (WMLs) demonstrating the central vein sign (ie, central vein sign-positive lesion [CVS+L]) and at least 1 paramagnetic rim lesion (PRL), representing perivenular lesion development and chronic active demyelination, respectively. Whether these imaging measures predict developing clinical multiple sclerosis (MS) in people with RIS is not yet known. Objective: To determine the prognostic value of various magnetic resonance imaging (MRI) measures, particularly PRLs and CVS+L, in predicting clinical MS in people with RIS. Design, setting, and participants: This was a multicenter prospective cohort study conducted from 2011 and 2024. Participants older than 18 years and fulfilling published RIS criteria were consecutively recruited from 3 large academic MS centers. Exposures: Participants underwent 3-T MRI including brain and spinal cord (SC) sequences and longitudinal clinical assessments. MRIs were evaluated for the total WML, PRL, and SC lesion (SCL) counts as well as the proportion of CVS+L. Main outcomes and measures: The primary outcome was the development of clinical symptoms of MS. Time-varying Cox regression assessed the association between PRLs and symptom onset. Elastic net regression identified key predictors, incorporating PRLs, age, sex, and SCL. Results: A total of 79 eligible people with RIS were included (36 [46%] in the discovery cohort [DC], 43 [54%] in the validation cohort [VC]). Of the initial 46 DC participants, 10 withdrew or were lost to follow-up, whereas all VC participants completed follow-up. In the DC (median [IQR] age, 40 [31-51] years; 25 female [70%]; median [IQR] follow-up, 6.4 [5.0-9.1] years), 9 of 36 people with RIS (25%) developed MS (median [IQR] time, 5.2 [5.0-6.8] years). In the VC (median [IQR] age, 43 [36-51] years; 23 female [53%]; median [IQR] follow-up, 4.4 [2.5-7.9] years), 9 of 43 people with RIS (21%) developed MS (median [IQR] time, 4.4 [2.5-4.7] years). Higher PRL count was associated with earlier symptom onset between 5 and 30 years after initial RIS diagnosis (hazard ratio [HR], 1.15; 95% CI, 1.05-1.26; P = .004) in the DC, replicated in the VC (HR, 1.51; 95% CI, 1.00-2.27; P = .04). In the DC, having 4 or more PRLs (odds ratio [OR], 14.64; 95% CI, 2.00-207.23; P = .02) and higher PRL count (OR, 1.15; 95% CI, 1.03-1.32; P = .02) predicted clinical MS. In the VC, having any PRL was significantly associated with developing clinical MS (OR, 20.90; 95% CI, 2.35-533.30; P = .02). Conclusions and relevance: Study findings suggest that accrual of nonresolving chronic inflammation in WML portends development of clinical MS in people with RIS, which may have clinical utility in guiding treatment decisions across the MS spectrum and strengthens the case for including asymptomatic MS in the diagnostic criteria. There is growing recognition that early detection of most chronic neurological diseases is critical to prevent or diminish future disability, and these findings are a specific example of how this principle might operate in practice. Sun, 01 Mar 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1561 2026-03-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1528 Glial Plasticity and Dysfunction : Mechanistic Insights and Therapeutic Opportunities in Neurodegeneration Correale, Jorge Recent advances, including single-cell transcriptomics, lineage tracing, and in vivo imaging, have unveiled the heterogeneity, plasticity, and functional versatility of astrocytes, microglia, oligodendrocytes, and Schwann cells. These cells respond to metabolic and immune cues, participate in synaptic regulation, and provide metabolic and trophic support to neurons. Their dual roles in neuroprotection and neurodegeneration underscore the complexity of their contributions across CNS disorders. This review examines the diverse physiological and pathological roles of glia, emphasizing their involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Mechanisms including metabolic dysfunction, inflammatory polarization, glial-immune crosstalk, and extracellular vesicle-mediated signaling are critically discussed. Emerging therapeutic strategies, ranging from glial reprogramming and senolytic therapies to the use of engineered extracellular vesicles and metabolic modulators, are evaluated for their potential to harness glial plasticity and mitigate disease progression. The review also outlines current challenges in translating glial biology into clinical interventions, including cellular heterogeneity, delivery barriers, and the need for specific biomarkers. A glia-centered therapeutic paradigm offers promising avenues to restore CNS homeostasis and promote regeneration in neurodegenerative diseases. Wed, 01 Apr 2026 00:00:00 GMT https://repositorio.fleni.org.ar/xmlui/handle/123456789/1528 2026-04-01T00:00:00Z