Globally, Alzheimer's disease (AD) is the leading cause of dementia. It is a long-term neurological condition that impairs memory, cognitive abilities, and behavioural stability. As per the Alzheimer's Association's 2023 report, approximately 60 million individuals live with dementia globally, and it is estimated that this number will be 139 million by the year 2050. The prevalence of AD continues to vary significantly across the world. In the United States alone, over 7 million individuals have AD, a number that is estimated to increase to almost 13 million by the year 2050. In Europe, around 11 million individuals have dementia, with AD being the leading cause. In Asia, especially in China and Japan, the ageing population has fuelled an acute rise in AD cases. China alone will have more than 18 million AD patients by 2050. Africa also has an emerging burden of AD due to increased life expectancy, with cases expected to double every two decades [1]. The disease's insidious onset places a substantial burden on caregivers and healthcare systems. Despite gains in research and awareness, AD remains a significant public health concern, emphasising the critical need for novel diagnostic and therapeutic approaches [2,3]. Most cases of dementia are due to AD. The current economic burden of AD on America is estimated to be $305 billion, and it is expected to surpass $1.1 trillion by 2050. AD is predicted to have a major financial impact as the population ages, underscoring the urgent need for workable management plans and viable therapies [4].

Significant advancements have been made in AD diagnosis in recent years. The Food and Drug Administration (FDA) authorized the Lumipulse G pTau217/Aß1-42 Plasma Ratio and other blood-based biomarker tests in May 2025 [5,6]. These blood-based biomarkers are used for the early detection of AD in the elderly. As compared to conventional techniques, viz., lumbar punctures and positron emission tomography (PET) scans, the blood-based biomarkers are more accurate and widely available [5,7]. Further, the diagnoses by blood tests have significantly improved with the use of ultrasensitive assay technologies like single-molecule arrays [5,8]. A new benchmark for AD diagnosis is being driven by advancements in neuroimaging methods and hybrid diagnostic models that incorporate imaging, blood-based biomarkers, and cognitive evaluations.

The pathophysiology of AD includes the buildup of internal neurofibrillary tangles (NFTs), including hyperphosphorylated tau, and also external to cells [9]. Pathologically, APP is abnormally processed to produce Aβ peptides, followed by the accumulation of Aβ in synaptic clefts, forming senile plaques, disrupting synaptic function, and causing neuroinflammation [10]. Meanwhile, Tau pathology develops within neurons, leading to hyperphosphorylated tau and NFTs, which lead to widespread synaptic loss and brain atrophy (Fig. 1) [11,12]. Brain function is affected by the formation of Aβ and NFTs, which is expected to result in synapse loss and ultimately neurodegeneration. Structural changes in the brain include the enlargement of ventricles due to cerebrospinal fluid accumulation and the progressive shrinkage of the hippocampus, a region critical for memory formation. These are the most important elements in determining a person's risk of developing AD. Several important factors influence an individual's risk of AD. These genetic variables included apolipoprotein E (APOE) ε4 allele, amyloid precursor protein (APP), and presenilin gene mutation. Further, lifestyle (unhealthy diet, smoking, and alcohol), environmental, and biological impacts can be roughly divided into modifiable and non-modifiable hazards [13]. The lack of accurate instruments for early AD diagnosis is a serious challenge in the struggle against the disease. Traditional techniques like clinical assessments and neuroimaging diagnose patients with significant pathological symptoms. This delay in diagnosis means that patients miss the opportunity for early intervention. To address this, there’s growing interest in identifying biomarkers that could help spot the disease sooner. Recent breakthroughs in imaging technology, such as PET scans, which reveal plaque buildup in the brain cells, show promise in enhancing the accuracy of Alzheimer's diagnosis, allowing for earlier detection. Over the last few decades, research has shifted toward generating small molecules that may act as both diagnostic instruments and therapeutic agents, a concept that is termed theranostics. This dual capability is beneficial for AD, where early detection remains difficult and effective therapies are scarce. Simultaneous diagnosis and treatment open the way for personalised medicine techniques that potentially transform the treatment of neurological disorders like dementia [14].

This review focuses on discussing the integration of molecular imaging with near-infrared (NIR) theranostic agents to enhance the early detection and therapy of AD. Existing diagnostic methods detect AD only after neuronal loss has occurred. Recent advances in chemical biology have led to the development of multifunctional small-molecule theranostic probes that combine diagnostic imaging and therapeutic action. It also emphasizes advances in biomarker studies and theranostic technologies aimed at enhancing early diagnosis and treatment efficacy. By integrating current understanding and new evidence, the review seeks to present a comprehensive picture of AD and highlight the need for novel interventions to address the growing burden on individuals and healthcare systems.