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BACKGROUND: The Rey Auditory Verbal Learning Test (RAVLT) assesses the long-term verbal episodic memory, while the short-term memory binding (STMB) tests assess conjunctive memory binding. In the STMB, participants should remember the integration of shapes (or objects) and colors, forming a unique representation in memory. OBJECTIVE: The objective of this study was to compare the STMB and the RAVLT as predictors of hippocampal atrophy. METHODS: All participants underwent neuropsychological assessment and MRI data were collected. Participants were 17 patients with mild cognitive impairment (MCI) and 12 patients with Alzheimer’s disease (AD). All participants performed the RAVLT test and two different paradigms of the STMB test: change detection and free recall. In the change detection task, patients need to recognize if there was a difference in shapes and colors (unbound) or shape-color integrations (bound) between two consecutive screens. In the free recall task, patients were asked to recall aloud objects and colors individually (unbound condition) or object-color integrations (bound condition) that they had just seen in a screen. The groups were compared using ANCOVA analyses, and regression analyses were used to evaluate which cognitive paradigm better predicted the hippocampal atrophy. RESULTS: 10 patients showed no hippocampal atrophy (all were MCI patients) and 19 had atrophy (7 MCI and 12 AD). The group with atrophy was older and showed worse performance in the cognitive tasks. The regression model using the atrophy (positive or negative) as the dependent variable, and the STMB tasks, RAVLT delayed score, age and education as the predictors, indicated that only the STMB change detection bound task was retained in the model (R = 0.517, R2 = 0.268, p = 0.004), explaining 26,8% of the variance. Present findings suggest that the change detection STMB task may be a better marker of neurodegeneration than the other tests.

IntroductionAlzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]).MethodsThe methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.ResultsAs the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC.DiscussionThe long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.

Diagnosing concomitant transverse myelitis (TM) and Guillain-Barré syndrome (GBS) can be challenging. We report a case of an elderly patient presenting with acute sensory and motor disturbances in the four limbs, associated with urinary retention, ophthalmoparesis, facial weakness, and dysarthria. Electrodiagnostic studies were consistent with acute motor sensory axonal neuropathy (AMSAN), and imaging showed a longitudinally extensive tumefactive contrast-enhancing hyperintense spinal cord lesion extending from T6 to the cone. Concomitant AMSAN and TM have not been previously reported in the elderly. Comorbid TM and other GBS variants have been previously reported. Intravenous methylprednisolone, plasma exchange, cyclophosphamide, or combination therapies are usually used, although there are no randomized controlled studies regarding treatment choices.

Objectives. Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a rare meningoencephalitis characterized by vasogenic edema and multiple cortical/subcortical microbleeds, shearing several aspects with the recently defined Amyloid-Related Imaging Abnormalities (ARIA) occurring in Alzheimer's disease (AD) passive immunization therapies. Here, we investigated the specific role of autologous anti-Aβ antibodies and Tissue Factor Pathway Inhibitor (TFPI) in order to identify novel biomarkers for ARIA. Methods. By a multicenter case-control study in 100 subjects, using a novel ultra-sensitive technique (patent application pending), we evaluated the anti-Aβ autoantibodies and TFPI, as a marker of cerebrovascular impairment, in the CSF of CAA-ri, CAA, AD, MS and controls. Levels of circulating Aβ40 (cAβ40), cAβ42, tau, P-181 tau and APOE4 genotype were also investigated. Results. We demonstrated a direct involvement of anti-Aβ autoantibodies during the occurrence of ARIA, showing that their concentration is specifically increased during the acute phase of CAA-ri (apCAA-ri) and progressively reduced with clinical and radiological remission. Moreover, a strong correlation with the increased mobilization of cAβ40 and cAβ42 during apCAA-ri was shown, followed by their return to control levels and reduced tau and P-181 tau after remission. A parallel increase of the endothelial impairment marker TFPI was also confirmed both in AD and apCAA-ri, in particular in those patients carrying the APOE4 allele . Conclusions. Our data strongly support the hypothesis that the pathogenesis of CAA-ri is mediated by a selective autoimmune reaction against cerebro-vascular Aβ, directly related to autoantibodies concentration and cAβ overloading. The parallel increase of TFPI during apCAA-ri may finally allows to speculate that ARIA is a temporary but necessary event preceding the downstream beneficial Aß-clearance effects of disease modifying therapies (DMTs), further strengthening the increased susceptibility to vascular damage by the therapeutically-administered antibodies. Given the similarities between spontaneous ARIA which develops in CAA-ri and that induced through immunization strategies, CSF anti-Aβ autoantibodies and TFPI may be proposed as useful biomarkers for the diagnosis of CAA-ri, and for a better stratification (at baseline) and the monitoring of ARIA during the upcoming DMTs prevention trials

Objective: cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined Amyloid-Related Imaging Abnormalities (ARIA) reported in Alzheimer’s disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid beta (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: we used a novel ultra-sensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibodies concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau and APOE4 genotype were also investigated. Results: during the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebro-vascular Aβ, directly related to autoantibodies concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA

Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri. Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated. Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel. Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.

Human prion diseases include Creutzfeldt-Jakob disease, Gerstmann-Stráussler-Scheinker disease, fatal familial insomnia, and kuru. Each of these diseases has a specific clinical presentation while spongiform encephalopathy, neuronal loss, and gliosis are their neuropathological hallmarks. We studied a Brazilian family with an autosomal dominant form of dementia. Nine members of the family were affected by a dementia with frontotemporal clinical features, with a mean age at onset of 44.8 +/- 3.8 years and a mean duration of symptoms of 4.2 +/- 2.4 years. Neuropathological examination of 3 patients showed severe spongiform change and neuronal loss in the deep cortical layers and in the putamen, but minimal gliosis in the most severely affected areas. The putamen and cerebellum, but not other areas of the affected brain, displayed prion protein immunoreactivity. A novel prion protein gene mutation causing a nonconservative substitution at codon 183 was identified in 2 neuropathologically confirmed affected individuals (mother and son). The mutation was transmitted in a mendelian fashion to 12 members of the family. Therefore, we identified a novel prion disease variant characterized by an early onset and long duration of the symptoms, severe spongiform change with minimal gliosis, associated with a prion protein gene mutation at codon 183.