Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Infection01:20

Infection

11.6K
When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
11.6K
Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

524
The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
524
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

676
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
676
Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

2.5K
The pathophysiology of pneumonia involves the following steps:
2.5K
Stages of Infection01:26

Stages of Infection

64.7K
Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
64.7K
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

2.6K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
2.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pathology and Genetics in a Global Cohort of Parkinsonian Disorders.

JAMA neurology·2026
Same author

Nicotinamide mononucleotide stimulates the activity of bursting slow-oscillation neurons in the supramammillary nucleus and enhances REM sleep.

iScience·2026
Same author

Identification of genetic modifiers of autosomal dominant Alzheimer's disease: a genome-wide association study.

The Lancet. Neurology·2026
Same author

A Non-Classical Neuroactive Steroid Exhibiting Potent, Efficacious GABA<sub>A</sub> Receptor Agonism and NMDA Receptor Inhibition.

bioRxiv : the preprint server for biology·2026
Same author

Pathology and genetics in a global cohort of Parkinsonian Disorders.

medRxiv : the preprint server for health sciences·2026
Same author

Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease.

The European journal of neuroscience·2026
Same journal

Evidence for progressive neurodegeneration in iatrogenic cerebral amyloid angiopathy.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Human brain connectome profiles mediate the relationship between pathology burden and clinical phenotypes in Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Kat5 cKO mouse replicates biological domain signatures associated with Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Evaluation of CSF and plasma tau species as fluid surrogate candidates for tau PET in prodromal to moderate Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Associations of self-reported obstructive sleep apnea with cognition and dementia risk in cognitively unimpaired middle-aged adults.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Inflammation profiles in Alzheimer's disease relate to cognition and neurodegeneration.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
See all related articles

Related Experiment Video

Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
09:07

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses

Published on: June 14, 2020

11.5K

Basic Science and Pathogenesis.

Mark Sands1, Bruno A Benitez2, Clare E Wallace3

  • 1Washington University School of Medicine, Elberton, GA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Lysosomal enzyme gene haploinsufficiency is linked to Alzheimer's disease (AD). Gene therapy targeting these enzymes shows promise in reducing amyloid-beta burden and improving cognitive function in AD models.

More Related Videos

A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
13:45

A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia

Published on: September 21, 2019

6.0K
Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
08:38

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses

Published on: February 22, 2019

6.3K

Related Experiment Videos

Last Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
09:07

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses

Published on: June 14, 2020

11.5K
A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
13:45

A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia

Published on: September 21, 2019

6.0K
Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
08:38

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses

Published on: February 22, 2019

6.3K

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Lysosome dysfunction is implicated in Alzheimer's disease (AD), but the specific pathogenic mechanisms remain unclear.
  • This study investigates the role of lysosomal enzyme gene haploinsufficiency in AD pathogenesis.
  • The potential of adeno-associated virus (AAV)-mediated gene transfer for treating AD is explored.

Purpose of the Study:

  • To determine if haploinsufficiency of lysosomal enzymes is associated with Alzheimer's disease.
  • To investigate the therapeutic potential of CNS-directed AAV-mediated gene transfer for AD.
  • To explore the impact of specific lysosomal enzyme gene heterozygosity on amyloid pathology.

Main Methods:

  • Genetic analysis of lysosomal enzyme genes in AD patients.
  • Proteomic analysis of brain tissue to identify activated pathways.
  • Murine models (PPT1 deficient and 5xFAD mice) to study gene dosage effects on amyloid-beta (Aβ) pathology.
  • AAV-mediated gene therapy in mouse models of AD.

Main Results:

  • Heterozygous mutations in lysosomal enzyme genes are enriched in AD patients.
  • The lysosomal storage disease pathway is activated in AD brains.
  • PPT1 heterozygosity in mice alters secretase activity, increases Aβ plaques and burden, and reduces lifespan.
  • AAV gene therapy in 5xFAD/PPT1+/- mice reduced Aβ burden, extended lifespan, and improved cognition.
  • Similar effects on Aβ pathology were observed for heterozygosity of NAGLU, GALC, IDUA, and GUSB genes.

Conclusions:

  • Heterozygosity of at least five lysosomal enzyme genes is strongly implicated in AD development.
  • These lysosomal enzyme genes represent potential therapeutic targets for genetically defined forms of AD.