Alzheimer’s disease Flashcards
What is Alzheimer’s?
A brain disorder that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks.
Those with the late-onset type symptoms first appear in their mid-60s.
What are clinical signs of Alzheimer’s?
Memory loss. Cognitive disturbances. Communication difficulties. Confusion and disorientation. Hallucinations. Impulsive behaviour. Difficulties in performing daily activities.
What is the neuropathology of Alzheimer’s?
Reduction in size of brain (particularly cerebral cortex, basal forebrain and hippocampus).
Presence of extracellular protein deposits (b-amyloid) - amyloid plaques.
Presence of tangled filaments within neurones- neurofibrillary tangles.
What is the beta-amyloid hypothesis?
The amyloid hypothesis postulates that amyloid-beta (Aβ), in a variety of forms, triggers a cascade harming synapses and ultimately neurons, producing the pathological presentations of Aβ plaques, tau tangles, synapse loss and neurodegeneration, leading to dementia.
What is the tau hypothesis?
The tau hypothesis states that excessive or abnormal phosphorylation of tau results in the transformation of normal adult tau into PHF-tau (paired helical filament) and NFTs.
Tau protein is a highly soluble microtubule-associated protein (MAP).
What is the presenilin hypothesis?
The presenilin hypothesis offers an alternative view of disease pathogenesis, proposing that PSEN1 mutations cause a loss of essential presenilin functions in the brain, which in turn triggers neurodegeneration and dementia in FAD3.
What is the APOE hypothesis?
Mediates cholesterol metabolism in an isoform dependent manner.
APOE is the main cholesterol transporter in the brain.
APOE4 isoform implicated in Alzheimer’s, atherosclerosis, cognitive impairment.
E4: is not a determinant of disease it is a risk factor.
E4: the largest genetic risk factor for late onset AD.
What is the calcium hypothesis?
Activation of the amyloidogenic pathway may function to remodel the neuronal Ca2+ signaling pathways responsible for cognition.
Hydrolysis of the beta-amyloid precursor protein yields two products that can influence Ca2+ signaling.
What is the free radical hypothesis?
The free radical hypothesis of aging, which was proposed many years ago, posits that the age-related accumulation of reactive oxygen species (ROS) results in damage to major components of cells: nucleus, mitochondrial DNA, membranes, and cytoplasmic proteins.
What is the neurotransmitter hypothesis?
This hypothesis suggested that a deficiency of the neurotransmitter norepinephrine (also known as noradrenaline) in certain areas of the brain was responsible for creating depressed mood.
What drugs are used to treat Alzheimer’s?
AChE-inhibitors:
Donepezil, rivastigmine, galantamine.
Limited efficacy in mild/moderate AD.
Problems - Liver toxicity and autonomic effects.
NMDA-receptor antagonist: memantine.
Anti-inflammatory drugs:
Aspirin and indomethacin.
Claimed to retard disease progress.
Oestrogen:
Hormone Replacement Therapy (HRT).
Claimed to reduce incidence of AD in women.
What is the mechanism of action of memantine?
Memantine works by blocking the receptors in the brain that glutamate would normally bind to.
This decreases the harmful effect of glutamate in the brain and may help improve your symptoms of dementia.
What is neprilysin?
Neprilysin (NEP) is the dominant Aβ peptide-degrading enzyme in the brain.
NEP becomes inactivated and down-regulated during both the early stages of AD and aging.
What is davunetide?
Davunetide is the first drug to improve memory performance by impacting the mechanisms that lead to physical damage in the brain caused by neurofibrillary tangles, one of the two established pathological hallmarks that are common to amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD).
Do statins help with Alzheimer’s?
The effects of statins may not only be affecting stroke risk, but may also be preventing microvascular infarcts that lead to dementia without an acute stroke.
Statins have been linked with reduced risk of all-cause dementia and even Alzheimer’s disease as well.
