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 back to main APP Mutations Directory
Updated 2 April 2010
View APP Mutations Diagram
by John Hardy, National Institute on Aging, Bethesda, MD, and Richard Crook, MD.,
Mayo Clinic, Jacksonville, FL.
Disease-associated intra-Aβ mutations
(courtesy of Dominic Walsh)
|
Mutation
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Phenotype
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Age of Onset
|
References
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E665D
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AD, but may not be pathogenic
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86?
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Peacock, et al., 1994
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KM670/671NL (Swedish)
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AD
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52 (44-59)
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Mullan, et al. 1992
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A673T
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Normal
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N/A
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Peacock, et al. 1993
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H677R
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AD
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55 (55-56)
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Janssen, et al. 2003
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D678N (Tottori)
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FAD
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60
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Wakutani, et al. 2004
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A692G (Flemish)
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Large dense core plaques linked to CAA
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40-60 but variable
|
Kumar-Singh et al,
2002
Hendriks, et al. 1992
Cras, et al. 1998
Roks, et al. 2000
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E693Δ
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AD
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Tomiyama et al., 2008
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E693G (Arctic)
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AD
Severe congophilic angiopathy, abundant amyloid plaques with a characteristic ringlike
character, no brain haemorrhage
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Age at disease onset ranged from 52 years to 65 years with a mean age of 56.9 (+/-1.1)
years
N/A
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Kamino et al., 1992
Nilsbeth et al., 2001
Basun et al., 2008
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E693K
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Cerebral Hemorrhage
|
?
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Tagliavini, et al. 1999 (no abstract avail.)
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E693Q (Dutch)
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HCHWA-D (a stroke syndrome)
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Typically ~50 but variable
|
Van Broeckhoven, et
al. 1990
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D694N (Iowa)
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AD or Cerebral Hemorrhage
|
69
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Grabowski, et al. 2001
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A713T
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AD, but may not be pathogenic
|
59
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Carter, et al., 1992
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A713V
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Schizophrenia: probably not pathogenic
|
?
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Jones, et al. 1992
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T714A (Iranian)
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AD
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52 (40-60)
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Pasaler, et al., 2002
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T714I (Austrian)
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Phenotype: Affects γ-secr cleavage directly, 11X increase in Aβ(42)/Aβ(40)
ratio in vitro. In brain, abundant and predominant nonfibrillar pre-amyloid plaques
composed primarily of N-truncated Aβ(42) in complete absence of Aβ(40).
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Kumar-Singh, et al.
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V715A (German)
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AD
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47
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De Jonghe, et al., 2001;
Cruts, et al., 2003
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V715M (French)
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AD
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52 (40-60)
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Ancolio, et al., 1999
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I716F
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|
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Guerreiro et
al., 2008
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I716T
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AD
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55
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Terrini, et al., 2002
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I716V (Florida)
|
AD
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55
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Eckman, et al., 1997
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V717F (Indiana)
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AD
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47 (42-52)
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Murrell, et al. 1991
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V717G
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AD
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55 (45-62)
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Chartier-Harlin, et
al. 1991
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V717I (London)
|
AD
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55 (50-60)
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Goate, et al. 1991
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V717L
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CSF tau and A-β consistent with AD; earlier onset than other 717 mutations
|
38
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Murrell, et al., 2000
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T719P
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AD
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46
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Ghidoni et al., 2009
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L723P (Australian)
|
AD
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56 (45-60)
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Kwok JB,
2000
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