Neuropathologically‐defined subtypes of Alzheimer's disease: Neurobiological subtypes of Alzheimer's disease. (7th December 2020)

• Record Type: Journal Article
• Authors: Murray, Melissa E
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.039957
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Neuropathologic studies have demonstrated the importance of recognizing atypical patterns of neurofibrillary tangle pathology in Alzheimer's disease (AD). Utilizing corticolimbic patterns to operationally classify neuropathologically‐diagnosed AD cases, we identified three subtypes: hippocampal sparing AD, typical AD, and limbic predominant AD (Murray 2011). While amyloid‐β plaque pathology does not differ across AD subtypes (Murray 2015), the frequency of co‐existing pathology does differ. Method: The FLorida Autopsied Multi‐Ethnic (FLAME) AD cohort was reviewed (Hanna Al‐Shaikh 2019). Co‐existing α‐synucleinopathies was examined, including Lewy body disease and the presence of amygdala predominant Lewy bodies which are often observed in the context of severe AD pathology. The severity of cerebrovascular disease was examined using the modified Kalaria score (Deramecourt 2012), which provides a score from 0‐10. Result: Out of 1361 AD cases, 175 (13%) were classified as hippocampal sparing AD, 1014 (74%) as typical AD, and 172 (13%) as limbic predominant AD. Limbic predominant AD cases were older at death (86 years) compared to typical AD (81 years) and hippocampal sparing AD (72 years) (p<0.001). A higher proportion of limbic predominant AD (26%) and typical AD (26%) had co‐existing Lewy body disease compared to hippocampal sparing AD (14%) (p=0.003). Amygdala predominant Lewy bodies were more frequently observed in limbic predominant AD (25%) compared to typical AD (17%) and hippocampal sparing AD (12%) (p=0.006). Limbic predominant AD has more severe cerebrovascular disease score (median=5, interquartile range 2‐6) compared to typical AD (4, 2‐6) and hippocampal sparing AD (4, 2‐5). Conclusion: Corticolimbic patterns of neurofibrillary tangle pathology provide key insight into the neurobiology underlying clinical heterogeneity of AD. We observed a greater frequency of co‐existing pathologies in limbic predominant AD and typical AD. Future biomarker studies and efforts of targeted therapeutics should consider the effect of multiple comorbid pathologies. It will be of great interest to examine how these co‐existing pathologies influence clinical progression and heterogeneity of clinical presentations in Alzheimer's disease patients.