Abstract
Alzheimer’s disease (AD) is a progressive neurological disorder that typically involves neuronal damage leading to the deterioration of cognitive and essential body functions in aging brains. Major signatures of AD pathology include the deposition of amyloid plaques and neurofibrillary tangles, disruption of the blood-brain barrier, and induction of hyper-activated proinflammation in the brain, leading to synaptic impairment and neuronal loss. However, conventional pharmacotherapeutic modalities merely alleviate symptoms, but do not cure AD, partly because drug screening has used model systems with limited accuracy in terms of reflecting AD pathology in human brains. In this regard, several AD organoids have received substantial attention as alternatives to AD animal models. In this review, we summarize the key characteristics required for the generation of a pathologically relevant AD brain organoid. We also overview major experimental organoid models of AD brains, such as spheroids, three-dimensional (3D) bioprinted constructs, and 3D brain-on-chips, and discuss their strengths and weaknesses for AD research. This review will provide valuable information that will inspire future efforts to engineer authentic AD organoids for the study of AD pathology and for the discovery of novel AD therapeutic strategies.
Highlights
Major signatures of Alzheimer’s disease (AD) pathology include the deposition of amyloid plaques and neurofibrillary tangles, disruption of the blood-brain barrier, and induction of hyper-activated proinflammation in the brain, leading to synaptic impairment and neuronal loss
We summarize the key characteristics required for the generation of a pathologically relevant AD brain organoid
Alzheimer’s disease (AD), the most common cause of dementia, is a worldwide public health concern that occurs in a meaningful proportion of elderly individuals [1]
Summary
Alzheimer’s disease (AD), the most common cause of dementia, is a worldwide public health concern that occurs in a meaningful proportion of elderly individuals [1]. Transgenic mice with mutations in amyloid beta (Aβ) precursor protein (APP) and/or presenilin (PS) are gold-standard AD model systems as they recapitulate signature aspects of AD, such as neuroinflammation and the deposition of Aβ and hyperphosphorylated-Tau (pTau) in the brain [3,4,5,6,7]. Despite these similarities, a number of discrepancies compared to human AD brains have been reported [8].
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