This review provides an updated overview of Alzheimer’s disease (AD), covering the major risk factors, disease mechanisms, diagnostic strategies, experimental models, and treatment progress shaping the field today. It explains that AD is the most common neurodegenerative disorder in older adults. It is defined pathologically by extracellular β-amyloid plaque buildup and intracellular hyperphosphorylated tau tangles. These changes are tied to progressive memory loss, cognitive decline, and behavioral symptoms. The paper also highlights important contributors to AD risk and progression, including APOE variants—especially APOE4—infections, chronic inflammation, vascular and metabolic conditions, and impaired amyloid clearance.

The review further shows how AD research is moving beyond symptom control toward earlier detection and disease-modifying treatment. In addition to traditional clinical evaluation and brain or cerebrospinal fluid biomarkers, researchers are increasingly studying peripheral biomarkers in high-risk populations to improve diagnosis and prediction. On the treatment side, the authors note that standard therapies can only temporarily ease symptoms. Newer amyloid-targeting drugs and emerging tau-focused strategies are aimed at modifying the disease itself. Even with this progress, the paper stresses that important challenges remain, including the incomplete understanding of sporadic AD, the lack of animal models that fully reproduce human disease, and the need for more effective therapies that can meaningfully slow or prevent progression.

Reference: Liu E, Zhang Y, Wang JZ. Updates in Alzheimer’s disease: from basic research to diagnosis and therapies. Transl Neurodegener. 2024 Sep 4;13(1):45. doi: 10.1186/s40035-024-00432-x. PMID: 39232848; PMCID: PMC11373277.

This review argues that GLP-1 receptor agonists, drugs originally developed for diabetes, are emerging as promising disease-modifying therapies for Parkinson’s disease (PD) and Alzheimer’s disease (AD). The author highlights early clinical evidence for several agents, including exendin-4/exenatide, liraglutide, and lixisenatide, noting that Phase II trials in PD showed improvements in motor and, in some cases, cognitive or quality-of-life measures that persisted even after treatment stopped. That persistence is presented as especially important because it suggests more than temporary symptom control and supports a possible neuroprotective or disease-modifying effect. The review also describes a Phase II trial of liraglutide in AD, where the drug appeared to slow cognitive decline and reduce loss of brain volume, calling this an important proof of concept that GLP-1–based therapies may help in both major neurodegenerative disorders.

A central theme of the article is that neurodegenerative diseases are too biologically complex to be treated successfully by targeting only one abnormal protein or pathway. Instead, the author argues that GLP-1 drugs may work because they affect multiple disease mechanisms at once, including impaired insulin signaling, chronic neuroinflammation, mitochondrial dysfunction, oxidative stress, synaptic failure, and defective autophagy. The review also suggests that newer dual GLP-1/GIP agonists designed to cross the blood-brain barrier more efficiently may prove even more effective than older diabetes drugs. Overall, the article presents GLP-1–based therapy as one of the most encouraging translational advances in the field, contrasting these early positive trials with the repeated failure of monoclonal antibody approaches against targets such as alpha-synuclein in PD.

Reference: Hölscher C. Glucagon-like peptide-1 class drugs show clear protective effects in Parkinson’s and Alzheimer’s disease clinical trials: A revolution in the making? Neuropharmacology. 2024 Jul 15;253:109984. doi: 10.1016/j.neuropharm.2024.109984. PMID: 38677445.

This review explains Alzheimer’s disease (AD) as a complex neurodegenerative condition driven by several overlapping mechanisms, including β-amyloid plaque formation, Tau protein hyperphosphorylation, oxidative stress, cholinergic dysfunction, genetic risk factors, and mitochondrial damage. The authors describe how amyloid deposits and Tau-related neurofibrillary changes contribute to neuronal injury, synaptic dysfunction, cortical and hippocampal atrophy, and progressive cognitive decline. They also emphasize that oxidative stress and mitochondrial dysfunction may accelerate neuronal death. Cholinergic system deterioration helps explain memory and neuropsychiatric symptoms seen in AD.

A major focus of the review is neuroinflammation, which the authors describe as both potentially protective and harmful. Microglia and astrocytes may initially help clear debris and respond to β-amyloid buildup, but chronic activation can sustain inflammation and worsen neuronal damage. The review highlights several inflammatory contributors, including β-amyloid–triggered complement activation, pro-inflammatory cytokines such as IL-1β and IL-6, cyclooxygenase activity, and immune-cell signaling. Overall, the authors suggest that better understanding and diagnosing neuroinflammation may open the door to more targeted AD therapies. In particular, they highlight approaches that may interrupt amyloid-driven inflammatory damage before irreversible neurodegeneration occurs.

Reference: Twarowski B, Herbet M. Inflammatory Processes in Alzheimer's Disease-Pathomechanism, Diagnosis and Treatment: A Review. Int J Mol Sci. 2023 Mar 30;24(7):6518. doi: 10.3390/ijms24076518. PMID: 37047492; PMCID: PMC10095343.0