Amyloid Hypothesis
This precursor protein is cleaved to produce AB peptide.
What is Amyloid Precursor Protein?
Tau aggregates are located in this part of the cell.
What is cytoplasm ?
Impaired insulin signaling in the hippocampus may disrupt this process underlying learning and memory, including long-term potentiation.
What is synaptic plasticity?
Glucose hypometabolism in Alzheimer disease can result in decreased production of this energy-storing molecule, causing neurons to struggle to maintain ion gradients, synaptic transmission, axonal transport, and protein homeostasis.
What is ATP?
These 2 Enzymes cleave a precursor protein to form to generate Amyloid beta protein.
What is beta and gamma secretase?
In alzheimer's disease, Tau becomes abnormally modified. This modification causes Tau to dissociate from microtubules and to aggregate.
What is hyperphosphorylation?
Insulin resistance may impair metabolism and clearance of this peptide, whose accumulation into extracellular plaques is characteristic of Alzheimer disease.
What is amyloid-beta (Aβ)?
Impaired mitochondrial electron transport in Alzheimer disease can increase electron leakage, contributing to lipid peroxidation, protein oxidation, and DNA damage through accumulation of these molecules.
What are reactive oxygen species (ROS)?
This isoform of amyloid-beta is especially pathogenic and it is a primary component of amyloid plaques in alzheimers.
What is AB42?
The tau hypothesis suggests that pathological tau is itself a central driver of neuronal dysfunction and neurodegeneration. Unlike extracellular amyloid plaques, aggregates of pathological tau form these intracellular structures characteristic of Alzheimer disease.
What is neurofibrillary tangles?
Insulin binding to its receptor normally activates this intracellular signaling cascade important for neuronal metabolism, survival, and synaptic function.
What is the IRS–PI3K–Akt pathway?
One of the metabolic abnormalities associated with AD is reduced glucose utilization in vulnerable brain regions. This can be visualized using this imaging modality.
What is FDG-PET?
In the Amyloid hypothesis, it is proposed that AB accumulation initiates a cascade involving synaptic dysfunction, tau pathology, glial activation, neuronal death, and eventually cognitive decline. For Patients with early onset Alzheimers, they may have a mutation in one of these 3 genes contributing to amyloid pathology.
Compared with amyloid-β plaque burden, the extent of pathology involving this protein correlates more closely with neuronal loss and cognitive impairment in Alzheimer disease.
What is Tau?
Brain insulin resistance decreases Akt signaling, reducing inhibition of this kinase that can phosphorylate tau.
What is GSK-3β?
Mitochondrial dysfunction in Alzheimer disease can impair buffering of this intracellular ion, whose excessive accumulation can disrupt synaptic signaling and activate pathways leading to neuronal injury.
What is Ca2+?
When looking at biomarkers for Alzheimers, amyloid beta measurement with this modality can be abnormal 20-25 years before symptoms occur.
What is CSF analysis (lumbar puncture)?
If performing a PET scan on a patient, you would want to use one of these two radioactive tracers to detect Tau.
What is Flortaucipir or Florquinitau?
Researchers have investigated delivering insulin through this route to target brain insulin signaling while minimizing systemic hypoglycemia
What is intranasal administration
Damage to neuronal mitochondria can cause release of this protein into the cytoplasm, activating caspases and promoting apoptotic neuronal death.
What is cytochrome C?