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by John Hardy, National Institute on Aging, Bethesda, MD, and Richard Crook, MD., Mayo Clinic, Jacksonville, FL.

Disease-associated Intra-A#&946; Mutations (Courtesy of Dominic Walsh)

Mutation	Phenotype	Age of Onset	References
Glu665Asp	AD, but may not be pathogenic.	86?	Peacock et al., 1994
Lys/Met670/Asn/Leu (Swedish)	AD	52 (44-59)	Mullan et al., 1992
Ala673Thr	Normal	N/A	Peacock et al., 1993
His677Arg	AD	55 (55-56)	Janssen et al., 2003
D678N	FAD	60	Wakutani et al., 2004
Ala692Gly (Flemish)	Large dense core plaques linked to CAA.	40-60, but variable.	Kumar-Singh et al., 2002 Hendriks et al., 1992 Cras et al., 1998 Roks et al., 2000
Glu693Gly (Artic)	AD, but may not be pathogenic. Reproduced plasma Aβ40 and 42, high protfibril levels.	58? N/A	Kamino et al., 1992 Nilsbeth et al., 2001
Glu693Gln (Dutch)	HCHWA-D (a stroke syndrome).	Typically ~50, but variable.	Van Broeckhoven et al., 1990
Glu693Lys (Italian)	Cerebral hemorrhage.	?	Tagliavini et al., 1999 (no abstract available)
Asp694Asn (Iowa)	AD or Cerebral hemorrhage.	69	Grabowski et al., 2001
Ala713Thr	AD, but may not be pathogenic.	59	Carter et al., 1992
Ala713Val	Schizophrenia, probably not pathogenic.	?	Jones et al., 1992
Thr714Ile (Austrian)	Affects γ-secretase cleavage directly, 11X increase in Aβ42/Aβ40 ratio in vitro. In brain, abundant and predominant nonfibrillar pre-amyloid plaques composed primarily of N-truncated Aβ42 in complete absence of Aβ40.		Kumar-Singh et al., 2000
Thr714Ala (Iranian)	AD	52 (40-60)	Pasaler et al., 2002
Val715Met (French)	AD	52 (40-60)	Ancolio et al., 1999
Val715Ala (German)	AD	47	De Jonghe et al., 2001; Cruts et al., 2003
Ile716Val (Florida)	AD	55	Eckman et al., 1997
Ile716Thr	AD	55	Terrini et al., 2002
Val717Phe (Indiana)	AD	47 (42-52)	Murrell et al., 1991
Val717Gly	AD	55 (45-62)	Chartier-Harlin et al., 1991
Val717Ile (London)	AD	55 (50-60)	Goate et al., 1991
Val717Leu	CSF tau and A-β consistent with AD; earlier onset than other 717 mutations.	38	Murrell et al., 2000
Leu723Pro (Australian)	AD	56 (45-60)	Kwok, 2000

Mutations in APP, PS1, and PS2 are also listed in the Alzheimer Disease Mutation Database (ADMD), maintained by Marc Cruts.