Abstract
The definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently that more sensitive immunohistochemistry for amyloid beta (Aβ) and hyperphosphorylated tau (HP-tau) replaced silver-staining techniques. However, immunohistochemistry against these and other proteins has not only allowed a more scientific evaluation of the pathology of AD but also revealed some mimics of HP-tau pathological patterns of AD, including age-related changes, argyrophilic grain disease and chronic traumatic encephalopathy. It also highlighted a number of cases of AD with significant additional pathology including Lewy bodies, phosphorylated TDP-43 (p-TDP-43) positive neuronal cytoplasmic inclusions and vascular pathology. This concomitant pathology can cause a number of challenges including the evaluation of the significance of each pathological entity in the make-up of the clinical symptoms, and the threshold of each individual pathology to cause dementia. It also raises the possibility of underlying common aetiologies. Furthermore, the concomitant pathologies could provide explanations as to the relative failure of clinical trials of anti-Aβ therapy in AD patients.
Highlights
Alzheimer’s disease is the most common cause of dementia in the Western world and is especially prevalent after 60 years of age
Aging-related tau astrogliopathy (ARTAG) is recently introduced terminology to describe age-related tauopathy changes within astroglial cells that are distinct from the glial tau pathology seen in well-characterised neurodegenerative diseases such as Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), argyrophilic grain disease (AGD) and globular glial tauopathy (GGT) [15,16,17,18]
Rather than relying on silver stains, a more scientific approach could be adopted when assessing the pathological patterns of Aβ and hyperphosphorylated tau (HP-tau)
Summary
Alzheimer’s disease is the most common cause of dementia in the Western world and is especially prevalent after 60 years of age. With the greater range of available antibodies and greater sampling of post-mortem brains, it has been shown that many patients with typical clinical AD features have the characteristic Aβ and HP-tau deposition in the form of plaques and tangles, respectively, and additional pathology. This includes infarcts or other cerebrovascular disease pathology, Lewy bodies, and TDP-43 pathology. It aims to provide some practical issues to assist with overall neuropathological diagnosis
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