Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease.

• Kinesin is a microtubule-associated motor protein that transports Alzheimer-associated amyloid precursor protein (APP) in neurons. In animal models, impaired kinesin-mediated APP transport seems to enhance formation of the neurotoxic 42 amino acid fragment of beta-amyloid (A beta 42). In man, one study suggests that a polymorphism (rs8702, 56,836G>C) in the kinesin light chain 1 gene (KNS2) may affect the risk of Alzheimer's disease (AD). To further assess KNS2 as a susceptibility gene for AD we analyzed 802 patients with sporadic AD and 286 controls, 134 longitudinally followed patients with mild cognitive impairment (MCI) and 39 cognitively stable controls for the rs8702 polymorphism. The rs8702 polymorphism did not influence risk of AD (p=0.46). However, rs8702 interacted with APOE epsilon 4 carrier status in AD (p=0.006) and influenced cerebrospinal fluid levels of hyperphosphorylated tau in MCI patients who converted to AD during follow-up (p=0.018). These findings support earlier indications that genetic variability in the KNS2 gene may play a role during early stages of AD pathogenesis.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Aged

Aged

80 and over

Alzheimer Disease

genetics

metabolism

pathology

Apolipoproteins E

genetics

Case-Control Studies

Disease Progression

Female

Gene Frequency

Humans

Male

Microtubule-Associated Proteins

genetics

Middle Aged

Phosphorylation

Polymorphism

Single Nucleotide

Protein Kinases

metabolism

Variation (Genetics)

physiology

tau Proteins

metabolism

apolipoprotein

biomarkers

polymorphism

Alzheimer's disease

kinesin

E

axonal transport

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)