Iatrogenic cerebral amyloid angiopathy

My name is Benedetta Storti. I am a neurologist at Carlo Besta Neurological Institute in Milan, Italy. I work in the Department of Cerebrovascular Disease and I have a special interest in small vessel pathology. In this presentation, I will discuss Iatrogenic Cerebral Amyloid Angiopathy which is an entity that has been known for only a few years. Iatrogenic cerebral amyloid angiopathy is considered to be clinically and pathologically identical to sporadic amyloid angiopathy. But on the contrary, it is not spontaneous and has a well-defined etiology. The underlying hypothesis is that there is a point of origin, a focus of the dissemination of amyloid. This seed consists of a dura patch applied during surgery several decades earlier. But let's start this interesting story from the beginning.

Misfolded proteins can form aggregates and induce a self-perpetuating process leading to the amplification and spreading of pathological protein assemblies. The intracerebral injection of prion protein-containing human brain homogenates into animals led to the discovery of transmissible prion disease approach in 1966. Proteins with this prion-like ability include alpha-synuclein, tau, TDP-43, but also amyloid-β. The observation that amyloid-β can seed from an exogenous source was tested in animals as early as 1993 in wild-type marmosets, a New World monkey that express a human-type sequence of amyloid-β. Intracerebral infusion of brain tissue material from an Alzheimer's disease patient resulted in amyloid-β deposits that could not be observed in control animals. Interestingly, the distribution pattern of exogenously induced plaques was similar to those in elderly uninjected controls that developed cerebral amyloidosis. Another strong evidence for prion-like seeding of misfolded amyloid-β aggregates in vivo was documented in experiments carrying out the inoculation of diluted brain extracts derived from confirmed Alzheimer's disease patients into young amyloid-β precursor protein transgenic mice. Most of those amyloid-β seeding studies were carried out in transgenic mice over-expressing mutant human amyloid precursor protein gene. Also, amyloid-β deposits can also be induced de novo in rodents that would never exhibits amyloid-β plaque pathology spontaneously within their normal lifespan. This is a strong indication that exogenously applied seeds act as a template for misfolding of endogenous amyloid-β and that seeding is not solely promoting the premature deposition of amyloid. In the work of Eisele,