Metals in Alzheimer’s Disease: A Combined Experimental and Numerical Approach
Pp. 100-147 (48)
Silvia Morante and Giancarlo Rossi
Alzheimer disease is a pathology causing severe problems with memory,
thinking and behavior. It accounts for the majority of dementia cases and is the sixth
leading cause of death in developed countries. Unfortunately a real cure is still missing
and the drug treatments today available can only reduce symptoms. It belongs to a large
class of diseases, called amyloidosis, in which endogenous proteins or peptides undergo
a misfolding process switching from the physiological soluble configuration to a
pathological fibrillar insoluble state. An important, but not yet fully elucidated, rôle
appears to be played in these processes by transition metals (mainly copper and zinc)
that have been observed to be present in fairly large amounts in patient's neurological
plaques. In this review we will show that the challenging problem of understanding the
physico-chemical basis of protein misfolding and aggregation can be successfully
investigated with a combination of modern spectroscopic techniques and advanced first
principle numerical simulations. In particular, it will be shown that different metals can
rival in peptide binding thus adding support to the hypothesis that metal dyshomeostasis
may be relevant in the Alzheimer disease development.
Amyloidosis, Aβ-peptide, ab initio molecular dynamics, metal ions,
X-ray Absorption Spectroscopy.
Dipartimento di Fisica, Università di Roma “Tor Vergata”, INFN, Sezione di Roma “Tor Vergata”, Via della Ricerca Scientifica, 00133 Roma, Italy.