Questionable “Alzheimer’s blood test” goes on sale prior to FDA approval

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First blood test to help diag­nose Alzheimer’s goes on sale (NBC News):

A com­pa­ny has start­ed sell­ing the first blood test to help diag­nose Alzheimer’s dis­ease, a leap for the field that could make it much eas­i­er for peo­ple to learn whether they have demen­tia. It also rais­es con­cern about the accu­ra­cy and impact of such life-alter­ing news.

Inde­pen­dent experts are leery because key test results have not been pub­lished and the test has not been approved by the U.S. Food and Drug Admin­is­tra­tion — it’s being sold under more gen­er­al rules for com­mer­cial labs.

The test is not intend­ed for gen­er­al screen­ing or for peo­ple with­out symp­toms — it’s aimed at peo­ple 60 and old­er who are hav­ing think­ing prob­lems and are being eval­u­at­ed for Alzheimer’s … It mea­sures two types of amy­loid par­ti­cles plus var­i­ous forms of a pro­tein that reveal whether some­one has a gene that rais­es risk for the dis­ease. These fac­tors are com­bined in a for­mu­la that includes age, and patients are giv­en a score sug­gest­ing low, medi­um or high like­li­hood of hav­ing amy­loid buildup in the brain.

The State of the Science:

a) In favor of the approach, co-authored by one of the devel­op­ers of the test: Amyloid‑B and Tau at the Cross­roads of Alzheimer’s Dis­ease (Advances in Exper­i­men­tal Med­i­cine and Biology).

  • Abstract: Alzheimer’s dis­ease (AD) is the most com­mon form of demen­tia char­ac­ter­ized neu­ropatho­log­i­cal­ly by senile plaques and neu­rofib­ril­lary tan­gles (NFTs). Ear­ly break­throughs in AD research led to the dis­cov­ery of amyloid‑B as the major com­po­nent of senile plaques and tau pro­tein as the major com­po­nent of NFTs. Short­ly fol­low­ing the iden­ti­fi­ca­tion of the amyloid‑B (AB) pep­tide was the dis­cov­ery that a genet­ic muta­tion in the amy­loid pre­cur­sor pro­tein (APP), a type1 trans­mem­brane pro­tein, can be a cause of auto­so­mal dom­i­nant famil­ial AD (fAD). These dis­cov­er­ies, cou­pled with oth­er break­throughs in cell biol­o­gy and human genet­ics, have led to a the­o­ry known as the “amy­loid hypoth­e­sis”, which pos­tu­lates that amyloid‑B is the pre­dom­i­nant dri­ving fac­tor in AD devel­op­ment. Nonethe­less, more recent advances in imag­ing analy­sis, bio­mark­ers and mouse mod­els are now redefin­ing this orig­i­nal hypoth­e­sis, as it is like­ly amyloid‑B, tau and oth­er patho­phys­i­o­log­i­cal mech­a­nism such as inflam­ma­tion, come togeth­er at a cross­roads that ulti­mate­ly leads to the devel­op­ment of AD.

b) Chal­leng­ing the basic approach: The case for reject­ing the amy­loid cas­cade hypoth­e­sis (Nature Neuroscience).

  • Abstract: Alzheimer’s dis­ease (AD) is a bio­log­i­cal­ly com­plex neu­rode­gen­er­a­tive demen­tia. Near­ly 20 years ago, with the com­bi­na­tion of obser­va­tions from bio­chem­istry, neu­ropathol­o­gy and genet­ics, a com­pelling hypoth­e­sis known as the amy­loid cas­cade hypoth­e­sis was for­mu­lat­ed. The core of this hypoth­e­sis is that it is patho­log­i­cal accu­mu­la­tions of amyloid‑B, a pep­tide frag­ment of a mem­brane pro­tein called amy­loid pre­cur­sor pro­tein, that act as the root cause of AD and ini­ti­ate its patho­gen­e­sis. Yet, with the pas­sage of time, grow­ing amounts of data have accu­mu­lat­ed that are incon­sis­tent with the basi­cal­ly lin­ear struc­ture of this hypoth­e­sis. And while there is fear in the field over the con­se­quences of reject­ing it out­right, cling­ing to an inac­cu­rate dis­ease mod­el is the option we should fear most. This Per­spec­tive explores the propo­si­tion that we are over-reliant on amy­loid to define and diag­nose AD and that the time has come to face our fears and reject the amy­loid cas­cade hypothesis.

The News in Context: