Alzheimer’s disease (AD) is diagnosed neuropathologically by the presence of amyloid beta (Aβ) plaques and tau neurofibrillary tangles. Aβ plaques accumulate 10 to 30 years before the onset of dementia and contribute to the spread of tau pathology across the brain. Although the exact mechanism linking Aβ and tau spread is unclear, it likely involves increased tau phosphorylation. Tau pathology spreads in a stereotypic order, potentially along four distinct trajectories, each associated with different clinical outcomes.
Current diagnostic methods for Alzheimer’s disease
Current diagnostic methods for AD include imaging and cerebrospinal fluid (CSF) biomarkers. Aβ PET scans and CSF Aβ levels are used to detect Aβ plaques, and tau PET scans, particularly with the flortaucipir tracer, to detect tau tangles. In terms of CSF biomarkers, Aβ42 and phosphorylated tau (p-tau) levels are crucial for diagnosing AD, with p-tau217 showing strong correlations with tau tangles and Aβ plaques.
Markers of neurodegeneration, such as hippocampal volume from MRI scans and CSF markers like total tau (t-tau) and neurofilament light (NfL), provide insights into the disease’s progression. NfL, in particular, reflects ongoing neurodegeneration and correlates with disease severity. While these biomarkers help guide diagnosis and prognosis, their use remains primarily in specialised settings, and blood-based biomarkers for AD are emerging as potential game-changers for more accessible and cost-effective diagnosis in both clinical practice and research.
