Alzheimer's disease

Abstract

Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

“…The remaining 95% of human AD is late onset (LOAD). The exact cause of LOAD remains unclear, although inflammation, oxidative stress, cholesterol metabolism, glycation, and other environmental and lifestyle factors are recognized as aggravating factors (Scheltens et al., 2016). …”

“…Major pathological features of the human AD brain include plaques of amyloid‐β made of cleaved APP, tangles of Tau proteins, and congophilic cerebral amyloid angiopathy (Kitazawa, Medeiros, & Laferl, 2012; Onos, Sukoff Rizzo, Howell, & Sasner, 2016; Sasaguri et al., 2016; Scheltens et al., 2016). With insufficient knowledge on the cause, modeling LOAD in rodents has been an issue.…”

Interleukin 1 Receptor and Alzheimer’s Disease-Related Neuroinflammation

“…Later, senile plaques and neuroibrillary tangles (NFTs), two typical protein depositions, were conirmed related to AD [10]. The main component of senile plaques is Aβ peptide; while NFTs are made from abnormal tau proteins [11]. A 42-amino acid long form of Aβ (Aβ42) was found as the main content in ibrillar Aβ peptides [12].…”

nNOS–CAPON interaction mediates amyloid‐β‐induced neurotoxicity, especially in the early stages

“…In pathology, abnormal accumulation of amyloid‐β (Aβ), dysfunction of synapses, and hyperphosphorylated tau are typical manifestations of Alzheimer's disease (Scheltens et al., 2016). Multiple mechanisms of Alzheimer's disease have been proposed among which the amyloid cascade hypothesis is the most popular.…”