This paper provides further data supporting the idea that immunization with N-terminal Aß peptides is effective at reducing plaque deposition and is associated with lower T cell activation potential, supporting the idea that this approach may provide as safer therapeutic vaccine for AD.

View all comments by Charles Glabe

I think that the explanation of microhemorrhages in the brain of vaccinated transgenic mice by the "washing out" of vascular or perivascular amyloid, and the recommendation of early treatment, "before amyloid deposition," is lacking rationale. Lumping all forms of vascular amyloid deposits into "CAA" does not take into account the difference between so-called "congophilic angiopathy," with amyloid inside the wall of medium-sized vessels, and "dysoric angiopathy," so named because amyloid seems to leak out of capillaries (in fact, the converse is probably true).

The first one is contemporary to the initiation of AD; I have seen it (Foncin, 1974; Foncin et al., 1985) in a cortical biopsy of a 42-year-old woman who died demented aged 51; she was the index case of FAD4 (Sherrington et al., 1995); congophilic angiopathy is seen prominently in AD with lobar hemorrhages. On the opposite, dysoric angiopathy is probably secondary.

My conclusion is what is called AD really is the result of the lumping together of various conditions with various pathogenies, and inferences for AD...  Read more

I think that the explanation of microhemorrhages in the brain of vaccinated transgenic mice by the "washing out" of vascular or perivascular amyloid, and the recommendation of early treatment, "before amyloid deposition," is lacking rationale. Lumping all forms of vascular amyloid deposits into "CAA" does not take into account the difference between so-called "congophilic angiopathy," with amyloid inside the wall of medium-sized vessels, and "dysoric angiopathy," so named because amyloid seems to leak out of capillaries (in fact, the converse is probably true).

The first one is contemporary to the initiation of AD; I have seen it (Foncin, 1974; Foncin et al., 1985) in a cortical biopsy of a 42-year-old woman who died demented aged 51; she was the index case of FAD4 (Sherrington et al., 1995); congophilic angiopathy is seen prominently in AD with lobar hemorrhages. On the opposite, dysoric angiopathy is probably secondary.

My conclusion is what is called AD really is the result of the lumping together of various conditions with various pathogenies, and inferences for AD therapy in general drawn from any particular mouse model are hazardous at best.

References:
FONCIN J.-F. (1974): Angiopathie amyloïde et maladie d'Alzheimer familiale. In "Biologie et pathologie des parois artérielles et artériolo-capillaires" Lyon, ACEML, pp. 49-50.

Foncin JF, Salmon D, Supino-Viterbo V, Feldman RG, Macchi G, Mariotti P, Scoppetta C, Caruso G, Bruni AC. Démence présénile d'Alzheimer transmise dans une famille étendue. Rev Neurol (Paris). 1985;141(3):194-202. Abstract

Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995 Jun 29;375(6534):754-60. Abstract

View all comments by Jean-François Foncin