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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'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...
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...
Parkinson's Disease: Overview01:15

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Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is to...
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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...

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Updated: May 28, 2026

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices
07:57

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices

Published on: April 11, 2018

Brain-First vs. Body-First Models in Neurodegenerative Disease: A Perspective Review.

Giuseppe Forte1, Maria Casagrande1

  • 1Department of Dynamic, Clinical Psychology and Health Studies, "Sapienza" University of Rome, 00185 Rome, Italy.

Neurosci
|May 27, 2026
PubMed
Summary
This summary is machine-generated.

Neurodegenerative diseases show varied progression, with brain-first and body-first models explaining cognitive decline heterogeneity. Understanding these distinct trajectories aids in future research and potential stratification.

Keywords:
autonomic dysfunctionbiomarkersbody-firstbrain-firstdementiadisease trajectoriesnarrative reviewneurodegenerative diseasesphenotypic heterogeneity

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Last Updated: May 28, 2026

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07:57

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Published on: April 11, 2018

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08:29

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Published on: December 18, 2016

Area of Science:

  • Neuroscience
  • Neurology
  • Pathology

Background:

  • Neurodegenerative diseases exhibit significant heterogeneity in cognitive decline.
  • Brain-first and body-first models offer frameworks for understanding disease variability.
  • These models differentiate phenotypes based on the primary site of pathology.

Purpose of the Study:

  • To synthesize evidence on brain-first and body-first neurodegenerative disease trajectories.
  • To propose an integrative conceptual framework for understanding phenotypic heterogeneity.
  • To identify research priorities for trajectory-based stratification.

Main Methods:

  • Narrative perspective review of existing literature.
  • Conceptual synthesis of central and peripheral biomarkers.
  • Integration of autonomic physiology and functional connectivity data.

Main Results:

  • Neurodegeneration is viewed as a dynamic interaction between central, peripheral, and network mechanisms.
  • Phenotypic heterogeneity can be interpreted through integrated biomarker and physiological data.
  • Evidence for distinct trajectories is currently associative and requires validation.

Conclusions:

  • A conceptual framework integrating central and peripheral factors can explain dementia heterogeneity.
  • Further research is needed to validate brain-first and body-first trajectories.
  • Trajectory-based stratification holds potential for future neurodegenerative disease research.