%0 Journal Article %J J Alzheimers Dis %D 2017 %T Adult-Onset Epilepsy in Presymptomatic Alzheimer's Disease: A Retrospective Study. %A DiFrancesco, Jacopo C %A Tremolizzo, Lucio %A Polonia, Valeria %A Giussani, Giorgia %A Bianchi, Elisa %A Franchi, Carlotta %A Nobili, Alessandro %A Appollonio, Ildebrando %A Beghi, Ettore %A Ferrarese, Carlo %X

BACKGROUND: The prevalence of epilepsy with onset in adulthood increases with age, mainly due to the accumulation of brain damage. However, a significant proportion of patients experience seizures of unknown cause. Alzheimer's disease (AD) is associated with an increased risk of seizures. Seizure activity is interpreted as a secondary event related to hyperexcitability caused by amyloid-β aggregation.

OBJECTIVE: Since neurodegenerative processes begin several years before clinical symptoms, epilepsy could be more frequent in the presymptomatic stages of dementia.

METHODS: We retrospectively reviewed the prevalence of epilepsy of unknown origin with adult onset before cognitive decline in a large cohort of AD patients (EPS-AD) recruited based on clinical and neuropsychological data. Data of patients with epilepsy followed by AD were compared with two control groups: patients with AD without seizures (no EPS-AD) and a large reference population (RP).

RESULTS: In AD patients, the prevalence of epilepsy of unknown origin, with onset in the adulthood before cognitive decline is 17.1 times higher compared with the RP (95% CI: 10.3-28.3). In EPS-AD, seizures begin on average 4.6 years (median 2.0) before the onset of cognitive symptoms and cognitive decline starts 3.6 years earlier compared with noEPS-AD.

CONCLUSIONS: Neurodegenerative processes of dementia could play a key role in the pathogenesis of epilepsy in a subgroup of individuals intended to develop cognitive decline. Adult-onset epilepsy of undefined cause could thus represent a risk factor for the ongoing neurodegenerative damage, even preceding by years the onset of clinical symptoms of dementia.

%B J Alzheimers Dis %V 60 %P 1267-1274 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/28968234?dopt=Abstract %R 10.3233/JAD-170392 %0 Journal Article %J Ann Neurol %D 2013 %T Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies. %A Piazza, Fabrizio %A Greenberg, Steven M %A Savoiardo, Mario %A Gardinetti, Margherita %A Chiapparini, Luisa %A Raicher, Irina %A Nitrini, Ricardo %A Sakaguchi, Hideya %A Brioschi, Monica %A Billo, Giuseppe %A Colombo, Antonio %A Lanzani, Francesca %A Piscosquito, Giuseppe %A Carriero, Maria Rita %A Giaccone, Giorgio %A Tagliavini, Fabrizio %A Ferrarese, Carlo %A DiFrancesco, Jacopo C %K Adult %K Aged %K Amyloid beta-Peptides %K Apolipoproteins E %K Autoantibodies %K Brain %K Case-Control Studies %K Cerebral Amyloid Angiopathy %K Female %K Humans %K Inflammation %K Male %K Middle Aged %K Peptide Fragments %K Phosphorylation %K Retrospective Studies %K Steroids %K tau Proteins %X

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.

%B Ann Neurol %V 73 %P 449-58 %8 2013 Apr %G eng %N 4 %R 10.1002/ana.23857