Forget sword and lance. It was a sharp mind that sliced through the genetics of neurodegenerative diseases. And it earned John Hardy, a lad from the town of Warrington in central England, a knighthood. Hardy and 1,277 others found themselves on the U.K.’s New Year Honours list for their contributions to politics, business, sports, entertainment—and science. Most received the Order of the British Empire, aka OBE. Hardy joins an elite group of 23 others who received knighthoods.
Hardy's award cites “Services to Human Health in Improving Understanding of Dementia and Neurodegenerative Diseases.”
Sir John helped establish the molecular biology of Alzheimer’s disease when he and his colleagues discovered a point mutation in the amyloid precursor protein that caused AD in a U.K. family (Goate et al., 1991). He helped formulate the amyloid cascade hypothesis, positing that Aβ deposition kick-starts a pathological cascade that leads to neurofibrillary tangles and eventually neuron loss and dementia (Hardy and Allsop 1991; Hardy et al., 1998). Though often embattled, the hypothesis still stands and draws support from new findings, including fluid and imaging biomarker data, and discovery of genetic variants that curb Aβ production and protect against AD (Sep 2021 news; Jul 2012 news).
Hardy’s quest to understand the genetics of neurodegeneration led to the identification of variants in the TREM2 gene that increase the risk for AD and frontotemporal dementia, to a triplication of the synuclein gene that causes Parkinson’s, and to numerous common variants that increase risk for AD discovered in large collaborations with other geneticists (Nov 2012 news; Oct 2012 news; Singleton et al., 2003; Mar 2019 news).
Hardy shared the Potamkin Prize in 1993, won the Lifesciences Breakthrough Prize in 2016, and shared the Brain Prize with Bart de Strooper, Michel Goedert, and Christian Haass in 2018 (Nov 2015 news; Mar 2018 news). The knighthood is his own. In a congratulatory announcement, friends and colleagues at the UK Dementia Research Institute cheekily anticipated seeing their knight in a suit.—Tom Fagan
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- Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991 Feb 21;349(6311):704-6. PubMed.
- Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991 Oct;12(10):383-8. PubMed.
- Hardy J, Duff K, Hardy KG, Perez-Tur J, Hutton M. Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau. Nat Neurosci. 1998 Sep;1(5):355-8. PubMed.
- Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841. PubMed.
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