A possible research direction for AmyloSENS

[Guest guest]

fyi

---------- Forwarded message ----------

From:

Date: Mon, May 26, 2008 at 12:11 AM

Subject: A possible research direction for AmyloSENS

To:

Ann Neurol. 2008 Mar 21;63(5):591-601. [Epub ahead of print] A nasal

proteosome adjuvant activates microglia and prevents amyloid deposition.

Frenkel D, Puckett L, Petrovic S, Xia W, Chen G, Vega J, Dembinsky-Vaknin

A, Shen J, Plante M, Burt DS, Weiner HL. Center for Neurologic Diseases,

Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

OBJECTIVE: We assessed whether peripheral activation of microglia by a

nasal proteosome-based adjuvant (Protollin) that has been given safely to

humans can prevent amyloid deposition in young mice and affect amyloid

deposition and memory function in old mice with a large amyloid load.

METHODS: Amyloid precursor protein (APP) transgenic (Tg) J20 mice received

nasal treatment with Protollin weekly for 8 months beginning at age 5

months. Twenty-four-month-old J20 mice were treated weekly for 6 weeks.

RESULTS: We found reduction in the level of fibrillar amyloid (93%),

insoluble beta-amyloid (Abeta; 68%), and soluble Abeta (45%) fragments in

14-month-old mice treated with Protollin beginning at age 5 months.

Twenty-four-month-old mice treated with nasal Protollin for 6 weeks had

decreased soluble and insoluble Abeta (1-40) and (1-42) and improved memory

function. Activated microglia (CD11b(+) cells) colocalized with Abeta

fibrils in the 24-month-old animals, and microglial activation correlated

with the

decrease in Abeta. No microglial activation was observed in 14-month-old

mice, suggesting that once Abeta is cleared, there is downregulation of

microglial activation. Both groups had reduction in astrocytosis. Protollin

was observed in the nasal cavity and cervical lymph node but not in the

brain.

Activated CD11b(+)SRA(+) (scavenger receptor A) cells were found in blood

and cervical lymph node and increased interleukin-10 in cervical lymph node.

No toxicity was associated with treatment. INTERPRETATION: Our results

demonstrate a novel antibody-independent immunotherapy for both prevention

and

treatment of Alzheimer's disease that is mediated by peripheral activation

of microglia with no apparent toxicity. Ann Neurol 2008;63:591-601.

PMID: 18360829

See what's new at Figure Photos & Anacostia Fine Art

Be my friend on MySpace http://www.myspace.com/figurephotos