Related Experiment Video

Updated: Jul 13, 2026

Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells
12:55

Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau Protein in Colorectal Cancer Cells

Published on: October 10, 2017

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

Malin E Andersson1, Annica Sjölander, Niels Andreasen

  • 1Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.

International Journal of Molecular Medicine
|July 6, 2007
PubMed

Insights

Genetic variations in the kinesin light chain 1 gene (KNS2) did not directly increase Alzheimer's disease (AD) risk. However, KNS2 rs8702 polymorphism impacts AD risk with APOE4 and influences tau levels in early disease stages.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Kinesin motor proteins transport amyloid precursor protein (APP) in neurons.
  • Impaired kinesin-mediated APP transport is linked to increased neurotoxic beta-amyloid (A beta 42) formation in animal models.
  • A prior study suggested a KNS2 gene polymorphism (rs8702) may influence Alzheimer's disease (AD) risk.

Purpose of the Study:

  • To investigate the role of the KNS2 rs8702 polymorphism as a susceptibility gene for sporadic Alzheimer's disease (AD).
  • To examine the interaction of rs8702 with APOE epsilon 4 carrier status in AD.
  • To assess the influence of rs8702 on cerebrospinal fluid (CSF) hyperphosphorylated tau levels in mild cognitive impairment (MCI) patients who progressed to AD.

Main Methods:

  • Genotyping analysis of the KNS2 rs8702 polymorphism in 802 sporadic AD patients and 286 controls.
  • Analysis of 134 longitudinally followed MCI patients and 39 stable controls.
  • Statistical analysis to determine the association of rs8702 with AD risk, APOE epsilon 4 interaction, and CSF tau levels.

Main Results:

  • The rs8702 polymorphism did not significantly influence the risk of developing AD (p=0.46).
  • A significant interaction was observed between rs8702 and APOE epsilon 4 carrier status in AD patients (p=0.006).
  • The rs8702 polymorphism affected CSF hyperphosphorylated tau levels in MCI patients who later converted to AD (p=0.018).

Conclusions:

  • Genetic variability in the KNS2 gene, specifically the rs8702 polymorphism, does not appear to directly increase AD risk.
  • The rs8702 polymorphism may play a role in AD pathogenesis through interaction with APOE epsilon 4.
  • KNS2 rs8702 influences early AD pathological changes, particularly tau phosphorylation, in individuals with MCI who progress to AD.

More Related Videos

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons10:38

Using Live-Cell Imaging to Measure the Effects of Pathological Proteins on Axonal Transport in Primary Hippocampal Neurons

Published on: December 22, 2023

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein09:22

In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

Published on: January 2, 2015

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Parkinson Disease ll: Pathophysiology01:24

Parkinson Disease ll: Pathophysiology

Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...