Background Previous studies have shown that in platelets of mild Alzheimer Disease (AD) patients there are alterations of specific APP forms, paralleled by alteration in expression level of both ADAM 10 and BACE when compared to control subjects. biochemical tests related to beta-amyloid cascade with ANNs allows a very good discrimination of AD in early stages, higher than that obtainable with classical statistics methods. Introduction Neurodegenerative diseases as Alzheimer Disease (AD) are posing a tremendous impact on our society. There is no remission in the progression, and pharmacological interventions available at present require an early and accurate identification of the disease . Up to now, buy BMN673 the diagnosis of probable and possible AD is based on neuropsychological evaluation by multidimensional assessments. Differential diagnosis between AD and other types of dementia is often based on exclusion . Thus, the possibility to use a biomarker supporting clinical diagnosis would be of great relevance in the early detection of the disease. For early AD diagnosis, an ideal diagnostic tool must be sensitive to earlier cognitive and biological changes, but is should be able to differentiate among AD, normal aging and other forms of dementia or pseudo dementia. It should be reliable, readily applicable and simple . In the last years, we have identified in easily accessible circulating cells, i.e. platelets, a combination of biological measurements that possess all characteristic to be considered as highly accurate biomarkers for AD [4-6]. In platelets it is possible to measure the levels of three molecular identities key-elements in the amyloid-cascade, namely Amyloid Precursor Protein (APP) forms as well as beta-secretase (beta-site- APP cleaving enzyme, BACE1) enzyme, responsible for amyloidogenic pathway, and alpha-secretase (ADAM10) responsible for non-amyloidogenic metabolism [7,8]. Further, we have demonstrated a concomitant and congruent modification of these biochemical parameters in platelets of buy BMN673 AD patients when compared to control subjects . Indeed, in platelets of mild AD patients we were able to show an alteration of specific APP forms, paralleled by a decreased expression level and activity of ADAM 10 as well as an increased BACE activity, when compared to control subjects . The simultaneous measurement of these biochemical parameters can be considered as a useful “combining strategy” to enhance the accuracy of the biological testing. However, this approach has intrinsic constrains, related to the statistical analysis used since classical statistics approaches suffer from underlying non linearity among variables. Artificial Neural Networks (ANNs) are adaptive models for the analysis of data which are inspired by the functioning processes of the human brain. They are systems which are able to modify their internal buy BMN673 structure in relation to a function objective. They are particularly suited for solving problems of the non linear type, being able to reconstruct the approximate rules that put a certain set of data C which describes the problem being considered C with a set of data which provides the solution . Thus, the aim of this study was to assess the efficacy of neural network in correctly classifying control subjects and mild AD patients only on the basis of peripheral beta-amyloid cascade biomarkers. Methods Subjects The study was carried out on 37 probable mild AD patients, and 25 healthy age-matched controls (CON), in accordance with local clinical research regulations and an informed consent was obtained. Each subject underwent a clinical and a standardized neuropsychological assessment for evaluation of cognitive functions, activities of daily living and behavioral and psychological disturbances. Probable AD diagnosis was based on National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association criteria (NINCDS-ADRDA) . Severity of dementia was rated according to Clinical Dementia Rating (CDR) scale, and only patients with CDR1 entered the study. The following exclusion criteria were applied: a) major depressive disorder, bipolar disorder, schizophrenia, substance use disorder, or mental retardation according to DSM-IV criteria; b) cerebro-vascular disorder, hydrocephalus, and intra-cranial mass, buy BMN673 documented by CT or MRI within the last 12 months; c) abnormalities in serum folate and vitamin B12, syphilis serology, or thyroid hormones’ levels; d) a history of traumatic brain injury or other neurological disease; e) significant medical problems (e.g. diabetes or hypertension; cancer; hepatic, renal, cardiac or pulmonary disorders). Further, subjects on psychotropic agents, nootropic drugs, cholinergic MAPK3 or anticholinergic agents, antiplatelets agents, anticoagulants, steroids, and serotoninergic drugs, were excluded unless they entered a wash-out phase lasting.