Amyloidosis

Question 1

Relevance of cleavage of amyloid precrusor protein

Answer 1

Abnormal cleavage of amyloid precursor protein leads to excess amyloid accumulation. APP mutations: increase B-secretase cleavase
PSEN1/PSEN2 mutations increase y(gamma?)-secretase activity

Question 2

Molecular Characteristics of Alzheimers Disease

Answer 2

• Amyloid plaques and neurofibrillary tangles accumulation
• .
• Formation of Amyloid Plaques: Cleavage of the amyloid precursor protein (APP) by beta and gamma secretase leads to formation of amyloid plaques in intercellular space
• Amyloid fibrils: different components but similar tertiary protein structures. AB(1-42) and tau build various fibril structures that differ in number/orientation/structure of strands.
• Cross-B sheet structure,
• amyloid state: Both tau and AB (1-42) have similar overall tertiary protein structure.
• Formation of neurofibrillary tangles: Misfolding of tau proteins leads to microtubule amyloid precursor protein and tau tangle formation.

Question 3

Diagnosis/Treatment

Answer 3

New research showing a single MRI scan of the brain could be enough to diagnose AD.
AB accelerated neurodegeneration caused by Alzheimers-associated ACE variant R1279Q rescued by angiotensin system inhibition in mice.
Lecanemad, donemab, remternetug: three most promising drugs
Prollin - new nasally administered AD vaccine heading for human clinical trials.

Question 4

New theory on the connection between alzheimers and amyloid connection

Answer 4

questions wether amyloiid precursor protein cuses AD or is just an accomplice in its molecular pathogenesis..?
researchers devised a multifunctional reporter for amyloid precusor protein tracking its localisation an dmobility and noticed an associated between the protein an dcholesterol that resides in the cell membrane of synapses.
Since cholestrol has a broad involvment in almost all aspects of neuron life - new theory on amyloid precursor proteins role in AD, especially in the surface of the synapses, that trigger neurodegeneration