Thin, Stubby or Mushroom: Spine Pathology in Alzheimer's Disease
Pp. 375-394 (20)
Since their first description by Ramon y Cajal at the end of the 19th century,
dendritic spines have been proposed as important sites of neuronal contacts and it has
been suggested that changes in the activity of neurons directly affect spine morphology.
In fact, since then it has been shown that about 90% of excitatory synapses end on
spines. Data indicate that spines are highly dynamic structures and that spine shape
correlates with the strength of synaptic transmission. Several mental disorders including
Alzheimer's disease (AD) are associated with spine pathology suggesting that spine
alterations play a central role in mental deficits. The aim of this review is to provide an
overview about the current knowledge on spine morphology and function as well as
about different experimental models to analyze spine changes and dynamics. The
second part concentrates on disease-relevant factors that are associated with AD and
which lead to spine alterations. In particular, data that provide evidence that Aβ
oligomers influence spine morphology and function will be presented and the
contribution of tau pathology will be discussed. The review ends with the discussion of
potential mechanisms how disease-relevant factors influence dendritic spines and
whether and how spine changes could be therapeutically suppressed or reversed.
Alzheimer’s disease, amyloid-beta, dendritic spines, NMDA receptor.