Studies in vivo and in vitro have suggested that the mechanism underlying Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between the cellular prion protein (PrPC) and amyloid-β oligomers (Aβo). This PrPC-Aβo complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P-Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD transgeni...

BACKGROUND Given the slow and variable clinical course of Alzheimer disease, very large and extended clinical trials are needed to identify a beneficial clinical effect of disease-modifying treatments. Therefore, biomarkers are essential to prove that an anti-β-amyloid (Aβ) drug candidate affects both Aβ metabolism and plaque load as well as downstream pathogenic mechanisms. OBJECTIVE To eval...

AIMS To improve early diagnosis of dementia disease, this study investigates correlates of cognitive complaints and cognitive test performance in patients with subjective (SCI) and mild (MCI) cognitive impairment. METHODS Seventy patients from a memory clinic, aged 45-79, with a score of 2 (n = 23) or 3 (n = 47) on the Global Deterioration Scale, were included. CSF biomarkers [Aβ42, total tau...

The computation of Kemeny rankings is central to many applications in the context of rank aggregation. Unfortunately, the problem is NP-hard. We show that the Kemeny score (and a corresponding Kemeny ranking) of an election can be computed efficiently whenever the average pairwise distance between two input votes is not too large. In other words, Kemeny Score is fixed-parameter tractable with r...

The computation of Kemeny rankings is central to many applications in the context of rank aggregation. Given a set of permutations (votes) over a set of candidates, one searches for a “consensus permutation” that is “closest” to the given set of permutations. Unfortunately, the problem is NP-hard. We provide a broad study of the parameterized complexity for computing optimal Kemeny rankings. Be...

One of the important neuropathological features of Alzheimer’s disease (AD) is the tau pathology seen as accumulation and hyperphosphorylation of this protein. Evidences showed that tau could be phosphorylated mostly at serine/threonine (S/T) residues by many kinases, including protein kinase B, glycogen synthase kinase (GSK)-3β, extracellular signal-regulated kinase (ERK1/2), ERK1/2 kinase (ME...

Significantly increased cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated at threonine 181 tau (p-tau) levels were frequently found in patients with mild cognitive impairment (MCI) who have an increased risk of developing Alzheimer's disease (AD). Though MCI often overlaps with depressive symptoms making early diagnosis difficult, to date no CSF marker has been probed to support th...

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This stu...

AIMS The aim of this study was to evaluate the diagnostic potential of cerebrospinal fluid (CSF) and serum levels of neurocytoskeletal proteins and their ratios for the diagnosis of dementias and to assess the differences in neurocytoskeletal proteins between neurodegeneration and neuroinflammation. METHODS CSF and serum levels of neurofilament light subunits (NFL) and neurofilament heavy sub...

Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers A...