Related Experiment Video
Updated: Jul 12, 2026
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Mechanisms of amyloid plaque pathogenesis
1Department of Health Sciences, Boston University, Boston, MA 02215, USA. fiala@bu.edu
Acta Neuropathologica
|September 7, 2007
Summary
Degenerating mitochondria in dystrophic neurites may cause amyloid plaque formation in Alzheimer's disease (AD). This revisits early theories, suggesting autophagosomes lead to amyloid production within neurites.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Early Alzheimer's disease (AD) research identified degenerating mitochondria in dystrophic neurites near amyloid plaques.
- The role of these organelles in plaque pathogenesis has been largely overlooked.
- Current hypotheses for amyloid plaque formation do not fully explain focal accumulation.
Purpose of the Study:
- To re-evaluate the role of degenerating mitochondria in Alzheimer's disease (AD) amyloid plaque pathogenesis.
- To explore the connection between disrupted axonal transport, autophagocytosis, and amyloid production.
Main Methods:
- Review of ultrastructural studies on Alzheimer's disease (AD).
- Analysis of evidence linking axonal transport disruption to mitochondrial degeneration and autophagosome accumulation.
- Integration of findings from aging, injury, and AD models.
Main Results:
- Disrupted axonal transport causes autophagocytosis of mitochondria without lysosomal degradation.
- Degeneration of these autophagosomes within dystrophic neurites may lead to amyloid production.
- This mechanism potentially explains focal amyloid accumulation in plaques.
Conclusions:
- The degeneration of mitochondria within dystrophic neurites is a significant factor in Alzheimer's disease (AD) amyloid plaque formation.
- This finding supports early hypotheses about the contribution of mitochondrial pathology to AD pathogenesis.
- Understanding this pathway may offer new therapeutic targets for Alzheimer's disease.
Related Concept Videos
03:03Amyloid 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...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid 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...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:23Alzheimer 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...
01:29Alzheimer 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...
01:30Atherosclerosis I: Introduction
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
01:24Parkinson 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...