%0 Journal Article %J J Alzheimers Dis %D 2023 %T Alzheimer's Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers. %A Milano, Chiara %A Hoxhaj, Domeniko %A Del Chicca, Marta %A Pascazio, Alessia %A Paoli, Davide %A Tommasini, Luca %A Vergallo, Andrea %A Pizzanelli, Chiara %A Tognoni, Gloria %A Nuti, Angelo %A Ceravolo, Roberto %A Siciliano, Gabriele %A Hampel, Harald %A Baldacci, Filippo %X

BACKGROUND: Neurosyphilis-associated cognitive and behavioral impairment- historically coined as "general paralysis of the insane"- share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer's disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-β deposition. Consequently, accurate classification and timely differential diagnosis may be challenging.

OBJECTIVE: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy.

METHODS: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases.

RESULTS: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD.

CONCLUSION: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.

%B J Alzheimers Dis %V 94 %P 611-625 %8 2023 Jul 18 %G eng %N 2 %R 10.3233/JAD-230170 %0 Journal Article %J J Alzheimers Dis %D 2022 %T The Role of Amyloid-β, Tau, and α-Synuclein Proteins as Putative Blood Biomarkers in Patients with Cerebral Amyloid Angiopathy. %A Piccarducci, Rebecca %A Caselli, Maria Chiara %A Zappelli, Elisa %A Ulivi, Leonardo %A Daniele, Simona %A Siciliano, Gabriele %A Ceravolo, Roberto %A Mancuso, Michelangelo %A Baldacci, Filippo %A Martini, Claudia %X

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer's disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids.

OBJECTIVE: The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.e., Aβ 1 - 40, Aβ 1 - 42, tau, and α-synuclein) levels in both red blood cells (RBCs) and plasma of CAA patients and HC, evaluating their role as putative peripheral biomarkers for CAA.

METHODS: For this purpose, the proteins' concentration was quantified in RBCs and plasma by homemade immunoenzymatic assays in an exploratory cohort of 20 CAA patients and 20 HC.

RESULTS: The results highlighted a significant increase of Aβ 1 - 40 and α-synuclein concentrations in both RBCs and plasma of CAA patients, while higher Aβ 1 - 42 and t-tau levels were detected only in RBCs of CAA individuals compared to HC. Moreover, Aβ 1 - 42/Aβ 1 - 40 ratio increased in RBCs and decreased in plasma of CAA patients. The role of these proteins as candidate peripheral biomarkers easily measurable with a blood sample in CAA needs to be confirmed in larger studies.

CONCLUSION: In conclusion, we provide evidence concerning the possible use of blood biomarkers for contributing to CAA diagnosis and differentiation from other NDs.

%B J Alzheimers Dis %V 89 %P 1039-1049 %8 2022 Sep 27 %G eng %N 3 %R 10.3233/JAD-220216 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology. %A Hampel, Harald %A Toschi, Nicola %A Babiloni, Claudio %A Baldacci, Filippo %A Black, Keith L %A Bokde, Arun L W %A Bun, René S %A Cacciola, Francesco %A Cavedo, Enrica %A Chiesa, Patrizia A %A Colliot, Olivier %A Coman, Cristina-Maria %A Dubois, Bruno %A Duggento, Andrea %A Durrleman, Stanley %A Ferretti, Maria-Teresa %A George, Nathalie %A Genthon, Remy %A Habert, Marie-Odile %A Herholz, Karl %A Koronyo, Yosef %A Koronyo-Hamaoui, Maya %A Lamari, Foudil %A Langevin, Todd %A Lehéricy, Stéphane %A Lorenceau, Jean %A Neri, Christian %A Nisticò, Robert %A Nyasse-Messene, Francis %A Ritchie, Craig %A Rossi, Simone %A Santarnecchi, Emiliano %A Sporns, Olaf %A Verdooner, Steven R %A Vergallo, Andrea %A Villain, Nicolas %A Younesi, Erfan %A Garaci, Francesco %A Lista, Simone %K Alzheimer Disease %K Animals %K Brain %K Humans %K Neurology %K Neurophysiology %K Precision Medicine %K Systems Biology %K Translational Medical Research %X

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

%B J Alzheimers Dis %V 64 %P S47-S105 %8 2018 %G eng %U https://content.iospress.com/download/journal-of-alzheimers-disease/jad179932?id=journal-of-alzheimers-disease%2Fjad179932 %N s1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29562524?dopt=Abstract %R 10.3233/JAD-179932 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study. %A Lista, Simone %A Toschi, Nicola %A Baldacci, Filippo %A Zetterberg, Henrik %A Blennow, Kaj %A Kilimann, Ingo %A Teipel, Stefan J %A Cavedo, Enrica %A Dos Santos, Antonio Melo %A Epelbaum, Stéphane %A Lamari, Foudil %A Dubois, Bruno %A Nisticò, Robert %A Floris, Roberto %A Garaci, Francesco %A Hampel, Harald %X

We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]. CSF neurogranin concentrations were significantly higher in AD patients compared with both HC subjects and FTD patients, suggesting that increased CSF neurogranin concentrations may indicate AD-related pathophysiology. CSF neurogranin was independently associated with both total tau and hyperphosphorylated tau proteins, whereas a non-significant correlation with the 42-amino acid-long amyloid-β peptide was evident. CSF neurogranin, however, was not superior to core AD biomarkers in differentiating HC from the three diagnostic groups, and it did not improve their diagnostic accuracy. We conclude that further classification and longitudinal studies are required to shed more light into the potential role of neurogranin as a pathophysiological biomarker of neurodegenerative diseases.

%B J Alzheimers Dis %V 59 %P 1327-1334 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/28731449?dopt=Abstract %R 10.3233/JAD-170368