Neurodegenerative diseases (NDDs) comprise a group of chronic, progressive disorders characterised by the gradual loss of neuronal structure and function within the central nervous system. Because mature neurons have limited regenerative capacity, cumulative injury results in irreversible deficits affecting cognition, behaviour, and motor control¹. Collectively, NDDs represent one of the fastest-growing causes of disability and healthcare burden worldwide.

Dementia accounts for the largest proportion of neurodegenerative disease burden. More than 55 million people globally are currently living with dementia, a figure projected to reach approximately 140 million by 2050³. Alzheimer’s disease (AD) is responsible for 60–70% of dementia cases, followed by vascular dementia, Lewy body disease, and other mixed pathologies³,⁴.

Alzheimer’s disease is a progressive neurodegenerative disorder characterised by memory impairment, executive dysfunction, behavioural change, and loss of independence. It is pathologically defined by amyloid-β plaques, hyperphosphorylated tau neurofibrillary tangles, synaptic dysfunction, and neuroinflammation⁵.

AD occurs predominantly in a sporadic form (>95% of cases), typically after age 65, while familial autosomal-dominant AD represents a rare subset associated with early onset due to specific genetic mutations⁶. Although advances in CSF, plasma, and PET biomarkers now allow biological characterisation during life, these tools remain resource-intensive and specialist-dependent, limiting broad population or longitudinal deployment⁷.

Parkinson’s disease is the second most common neurodegenerative disorder, affecting more than 8.5 million people worldwide⁸. It is characterised by degeneration of dopaminergic neurons and accumulation of α-synuclein pathology, resulting in motor and non-motor symptoms. Diagnosis remains clinical, as no single blood-based or imaging test definitively confirms PD in routine practice⁹.

Chronic traumatic encephalopathy (CTE) is a progressive tauopathy associated with repetitive head impacts, including concussive and sub-concussive trauma. While most commonly described in contact-sport athletes and military populations, CTE is not restricted to these groups¹⁰.

CTE is currently diagnosable only post-mortem, based on a distinct pattern of perivascular tau deposition that differs from Alzheimer’s disease¹⁰,¹¹. Clinical features may include executive dysfunction, memory impairment, mood disturbance, impulsivity, aggression, and eventual dementia, often emerging years to decades after exposure¹¹.

Although a causal link between repetitive mild TBI and later neurodegeneration has not yet been definitively proven in living individuals, epidemiological and mechanistic evidence increasingly supports TBI as a risk modifier for later-life neurodegenerative disease, including AD, PD, and other dementias¹².

Traumatic brain injury—particularly mild, repetitive, or blast-related injury—initiates a cascade of neuroinflammatory, metabolic, vascular, and synaptic changes. While many individuals recover clinically, a subset experience persistent dysregulation that may contribute to long-term neurodegenerative processes¹²,¹³.

Critically, these processes are not disease-specific. Neuroinflammation, altered protein homeostasis, mitochondrial dysfunction, and synaptic loss are shared pathological mechanisms across TBI, AD, PD, and CTE¹³. This convergence suggests the existence of common upstream biological signals that may be detectable well before overt clinical disease emerges.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression and play a central role in neuronal development, synaptic plasticity, inflammation, and cellular stress responses. Importantly, miRNAs are:

• Biologically stable in blood
• Sensitive to brain injury and neurodegenerative processes
• Capable of reflecting dynamic, longitudinal changes rather than static pathology¹⁴,¹⁵

Growing evidence demonstrates overlapping miRNA signatures across TBI, Alzheimer’s disease, Parkinson’s disease, PTSD, and other neurodegenerative conditions, supporting their potential as cross-cutting biomarkers of neurobiological injury and risk¹⁴–¹⁶.

Rather than diagnosing a single disease in isolation, miRNA-based approaches may enable:

• Earlier detection of pathological brain responses
• Risk stratification following TBI
• Longitudinal monitoring of recovery or progression
• Objective biological context to complement clinical assessment
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The convergence of traumatic brain injury and neurodegenerative disease biology highlights a critical diagnostic gap: current tools detect disease late, when neuronal loss is already advanced. Objective, scalable biomarkers capable of capturing early molecular dysregulation are essential to shift care toward prevention, monitoring, and timely intervention.

miRNA-based platforms represent a promising pathway to address this unmet need—offering a biologically grounded approach that may unify assessment across acute injury, chronic symptoms, and long-term neurodegenerative risk.