Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis

Abstract

Down syndrome (DS) is the main genetic cause of intellectual disability worldwide. The overexpression of the Amyloid Precursor Protein, present in chromosome 21, leads to β‐amyloid deposition that results in Alzheimer disease (AD) and, in most cases, also to cerebral amyloid angiopathy (CAA) neuropathology. People with DS invariably develop the neuropathological hallmarks of AD at the age of 40, and they are at an ultra high risk for suffering AD‐related cognitive impairment thereafter. In the general population, cerebrovascular disease is a significant contributor to AD‐related cognitive impairment, while in DS remains understudied. This review describes the current knowledge on cerebrovascular disease in DS and reviews the potential biomarkers that could be useful in the future studies, focusing on CAA. We also discuss available evidence on sporadic AD or other genetically determined forms of AD. We highlight the urgent need of large biomarker‐characterized cohorts, including neuropathological correlations, to study the exact contribution of CAA and related vascular factors that play a role in cognition and occur with aging, their characterization and interrelationships. DS represents a unique context in which to perform these studies as this population is relatively protected from some conventional vascular risk factors and they develop significant CAA, DS represents a particular atheroma‐free model to study AD‐related vascular pathologies. Only deepening on these underlying mechanisms, new preventive and therapeutic strategies could be designed to improve the quality of life of this population and their caregivers and lead to new avenues of treatment also in the general AD population.

Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

“…The second gene with the greatest level of association was MIR9-2. Although MIR9-2 has not been related to periodontal disease or other oral diseases in the literature, a close association has been reported between this gene and Alzheimer's disease, whose prevalence is especially high among individuals with DS [29]. MIR9-2 is directed at two of the most important proteins in the etiopathogenesis of Alzheimer's disease: the amyloid-beta precursor protein (APP), which transports the amyloid-β peptide that precipitates in amyloid plaques, and β-Site APP cleaving enzyme 1 (BACE1), which cleaves the APP to originate amyloid beta.…”

Down syndrome: the prevalence of Alzheimer’s disease and the role of thyroid hormone

“…In DS, the APP gene is tripled since it is located on chromosome 21. Moreover, other genes encoded by chromosome 21 are more associated with cognitive worsening than APP (CARMONA-IRAGUI et al, 2019). Therefore, DS is a genetic example of increased production of Aβ, making this group interesting for the study of AD (ANNUS et al, 2016).…”

Diagnosis and treatment of localized AL-amyloidosis

“…Наиболее многочисленной является группа локального церебрального амилоидоза -депозиция β-белка (Аβ-амилоидоз) приводит к болезни Альцгеймера и синдрому Дауна (синтез β-белка кодируется 21 хромосомой, а трисомия этой хромосомы приводит к гиперпродукции этого белка и его отложению в виде амилоида в головном мозге) [5], депозиция прионового белка является причиной губкообразных энцефалопатий (куру, болезнь Крейтцфельда-Якоба, фатальная семейная бессонница, синдром Гертсманна-Штраусслера-Шейнкера), известны наследственные формы амилоидной ангиопатии мозговых сосудов с развитием кровоизлияний (ACys-амилоидоз -цистатиновый, ABri-амилоидоз) [6]. Самой частой формой локального амилоидоза является амилоидоз пред сердий, обусловленный отложением предсердного натрийуретичес кого фактора (AANF-амилоидоз) [7].…”