Related Experiment Video

Updated: Jul 15, 2026

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
12:28

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains

Published on: June 3, 2020

Pathological tau tangles localize to focal cortical dysplasia in older patients

Arjune Sen1, Maria Thom, Lillian Martinian

  • 1Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London, UK.

Epilepsia
|April 20, 2007
PubMed
Abstract

Insights

Focal cortical dysplasia (FCD) in older individuals shows increased susceptibility to tau tangles, suggesting a link between developmental abnormalities and age-related neurodegeneration.

Area of Science:

  • Neuroscience
  • Pathology
  • Developmental Biology

Background:

  • Neurodevelopmental processes, like those involving cyclin-dependent kinase 5 (cdk5) and glycogen synthase kinase 3 beta (GSK3beta), can contribute to neurodegeneration.
  • These kinases are crucial for cortical development but can also hyperphosphorylate tau, potentially driving Alzheimer's disease pathogenesis.
  • Focal cortical dysplasia (FCD) involves dysplastic neurons with increased cdk5 and GSK3beta, and neurofilament accumulations, indicating a neurodevelopmental origin of epilepsy.

Purpose of the Study:

  • To investigate if the developmentally abnormal cortex in FCD is more vulnerable to tau-mediated neurodegeneration compared to adjacent normal cortex.
  • To explore the relationship between FCD, tau pathology, and age-related neurodegenerative changes.

Main Methods:

  • Examined 15 FCD cases across a wide age range.
  • Utilized silver staining and immunohistochemistry (tau, AT8, RD3, RD4) to detect beta-amyloid, phosphorylated tau, and neurofibrillary tangles.
  • Employed two-dimensional cell counting to quantify cellular changes.

Main Results:

  • Beta-amyloid plaques, hyperphosphorylated tau, and neurofibrillary tangles were observed exclusively in older patients.
  • Pathological tau tangles were localized specifically within the dysplastic neurons of FCD.
  • Immunoreactivity for 3- and 4-repeat tau was also restricted to FCD regions in older individuals.
  • With advancing age, FCD cortex showed reduced cellularity, and a greater percentage of dysplastic neurons exhibited pathological tau phosphorylation.

Conclusions:

  • Older patients with FCD demonstrate heightened susceptibility to developing pathological tau neurofibrillary tangles compared to unaffected adjacent cortex.
  • These findings suggest a novel convergence point where abnormal neurodevelopmental processes intersect with age-related neurodegenerative pathways.
  • This study highlights a potential mechanism linking developmental brain abnormalities to later-life neurodegenerative pathologies.

More Related Videos

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...
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...
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Dementia l: Introduction01:22

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...