Amyloid beta in hereditary cerebral hemorrhage with amyloidosis-Dutch type

作者：Kamp Juliette A; Moursel Laure Grand; Haan Joost; Terwindt Gisela M; Oberstein Saskia A M J Lesnik; van Duinen Sjoerd G; van Roon Mom Willeke M C^*

来源：Reviews in the Neurosciences, 2014, 25(5): 641-651.

DOI：10.1515/revneuro-2014-0008

• Alzheimer%26apos
• s disease
• amyloid precursor protein
• amyloidosis
• cerebral amyloid angiopathy
• Dutch mutation

Hereditary cerebral hemorrhage with amyloidosis Dutch type is an autosomal dominant hereditary disease caused by a point mutation in the amyloid precursor protein gene on chromosome 21. The mutation causes an amino acid substitution at codon 693 (E22Q), the %26apos;Dutch mutation%26apos;. Amyloid beta, the product after cleavage of the amyloid precursor protein, is secreted into the extracellular space. The Dutch mutation leads to altered amyloid beta cleavage and secretion, enhanced aggregation properties, higher proteolysis resistance, lowered brain efflux transporter affinity, and enhanced cell surfaces binding. All these result in amyloid beta accumulation in cerebral vessel walls, causing cell death and vessel wall integrity loss, making cerebral vessel walls in hereditary cerebral hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction, leading to hemorrhages and infarcts. Studying the effects of altered amyloid beta metabolism due to mutations like the %26apos;Dutch%26apos; provides us with a better understanding of amyloid beta toxicity, also in other amyloid beta diseases like sporadic cerebral amyloid angiopathy and Alzheimer%26apos;s disease.

• 出版日期2014-10