Amyloid, The Amyloid B -Peptide and Alzheimer’s Disease: Structural Considerations - Molecules: Nucleation, Aggregation and Crystallization - page 286

polymerize into amyloid fibrils. An emerging view is that a low net
charge, unstructured regions, exposed β -sheets and residues with a high

-sheet propensity (Thr, Ile, Tyr, Phe or Val) favors amyloid formation
(Dobson et al ., 2003; Tjernberg et al ., 2002).
The structure of amyloid is very stable, and harsh conditions such as
treatment with formic acid or high concentrations of guanidine are needed
to dissolve the fibrils. Likewise, the fibrils are resistant to proteolytic
degradation and can therefore accumulate over time. Although the fibrils
are relatively well characterized, little is known about the processes
leading to their formation. Here, we will focus on the amyloid found in
Alzheimer's disease, since it is the most studied.

β

Amyloid in Alzheimer's Disease

Alzheimer's Disease (AD) is a progressive neurodegenerative disease,
affecting around 24 million people worldwide. Age is the most important
risk factor for AD, and thus, the number of affected individuals will rise
rapidly as the mean life expectancy of the human population increases.
The first sign of the disease is forgetfulness, followed by loss of cogni-
tive functions and changes in personality. Eventually, the patient needs
constant care and becomes bedridden. There is currently no cure for AD,
but treatment with acetylcholine esterase inhibitors can in many cases
have a beneficial effect and attenuate the progress of the disease for a
limited time.
The disease was first described in 1906 by the German physician
Alois Alzheimer. In silver stained sections from a demented patient's
brain, he observed what today is known as the pathological hallmarks
of AD: extracellular plaques and intraneuronal fibrils. Almost 80 years
later, a breakthrough in AD research came with the discovery that the
amyloid found in AD was composed of the amyloid )

(Glenner et al ., 1984; Masters et al ., 1985). Extensive research followed
this discovery, and the A

β -peptide (A β

precursor protein (APP) was cloned a couple
of years later, while the proteases responsible for processing APP into

β