SD

A former Navy SEAL and firearms expert writes aboutwhy there should be changes to current gun laws and

discusses the importance of gun safety.SD4

AIMING FOR CHANGE

GOOD WEEK

Park party!: Billy Joel returns toSan Diego for the first time in 15years with a May 14 concert atPetco Park. Big-shot ticket presalesstart Monday. The rest of youse canwait until Friday.

Al fresco tunes: The San DiegoSymphony wins approval for apermanent waterfront concertvenue on Embarcadero Marina ParkSouth. The moon approves.

Stroke hopes: Scientists fromCarlsbad’s Ionis Pharmaceuticalsfind that an experimental drugdesigned to reduce damage fromstrokes shows promise in animaltesting. Fingers crossed! Paws, too.

Apple: The number of paid AppleMusic subscribers hits the 10 mil-lion mark after just six months, atotal Spotify took six years to reach.There’s gold in those streams.

Pachyderms: The Ringling Bros.

and Barnum & Bailey circus willend its Asian elephant act in May,and the elephants will retire toFlorida. We’ll be needing biggerearly bird specials.

BAD WEEK

Dean Spanos:What wasbehind NFLDoor No. 1?No Carsonstadium forthe Chargersowner. We feelfor you. Ex-cept that wetotally don’t.

Rock lovers: David Bowie dies atthe age of 69, leaving a titanicmusical legacy and a flood ofshock and loss. Rebel rebel, we’rekind of a mess.

CVS: Fresh & Easy’s plan to sellits Point Loma lease to CVS is puton hold when neighbors objectand the owner balks. Bring on thegeneric analgesics.

Gossip Inc.: The anonymouscomplaint about local Immigra-tion and Customs Enforcementworkers being recruited for sexparties turns out to be false.Some people are no fake fun atall.

Golden Globes: Viewership of thisyear’s Golden Globe Awards broad-cast was down 4 percent from lastyear. In the nasty spirit of host RickyGervais, we blame Ricky Gervais.

KARLA PETERSON • U-T

GOODWEEK /BADWEEK Your news score card

The human brain is the most complexobject on Earth, and what causes thisseat of consciousness to slowly and ir-reversibly deteriorate from Alzheim-er’s disease is one of science’s greatestmysteries.

We still don’t know how to stop Alz-heimer’s or reverse the degeneration it

causes, and time is of the essence as America’s agingpopulationmeansanexplosion in thenumberofpeoplewith the affliction.

But we’ve also made unprecedented progress inlearning about Alzheimer’s — what it is, how to diag-nose it and evenhow to lower the odds of contracting it.Experts increasingly stress that the lifestyle tools for

building up long-lasting, protective brain power mustbe used decades before anymental decline appears. Inother words, it’s foolish to think only seniors and the el-derly shouldworry about thedisease.

There’s also risinghopeon the treatment front:Nev-er before has lab research led to asmany experimentaltherapies being tried in Alzheimer’s patients, and rightbehind them is a growing list of other potentialmedica-tionsbeing readied for testing inpeople.

As the mystery is lifting, so is the sense of helpless-ness. Much of this demystifying work is taking place inSanDiego,whichhasbeenavibrant, internationally re-spected center ofAlzheimer’s research for decades.

Here’sa lookatthe latestdiscoveriesaboutAlzheim-er’s, newest strategies forbattling thediseaseandmostauthoritativeadviceonhowtopreserveyourbrainpow-er.

Magnified image showshow Alzheimer’s diseasesevers importantconnections betweenneuron cells in the brain.NATIONAL INSTITUTEON AGING

N E W H O P E

A G A I N S T

A L Z H E I M E R ’ S

SECTION SUNDAY • JANUARY 17, 2016

San Diegoresearchersstudy howboosting

brain activity,early drugtherapies

can ward offdisease

BY BRADLEY J. FIKES

SEE RESEARCH • SD2

Appetite for learningMore than ever, scien-

tists agree that one of themost important ways toward off Alzheimer’s andother aging-related mentaldeclines is to strengthenyour ability to analyze,imagineandprocessnewin-formation, much as youwould strengthen yourmuscles with workouts atthe gym.

The idea is to stretchyour thinking by engagingin cognitively demandingtasks such as acquiring anadditional skill, learning asecond language and evenadjusting to a different pro-fession. Studies have foundthat fundamental cognitiveskills such as memory in-crease when people exposetheir brains to these com-plex, unexplored territoriesof thought.

“If you learn somethingnew, you build upmore syn-apses in the brain,” said Dr.Mark Tuszynski, director ofUC San Diego’s Center forNeuralRepair.

While it helps to consis-tently work out your brainfromchildhoodonward, youdon’t have to be young tobenefit. Older people im-prove theirmemorybypick-ing up skills that requireconstant use of memoryand reasoning, researchhasshown.

This ageless benefitpoints to the much-dis-cussed topic of neuroplas-ticity — the ability of thebrain to adapt by rewiringitself. When parts of thebrain are damaged, as in a

stroke, other parts learn tocompensate. And contraryto long-held dogma, theadult brain can create newneuron cells.

Sophisticated concep-tual work and even physicalexercise have been found toincrease that regenerativefeature. Scientists are try-ing to devise new treat-ments to further stimulatethis self-repair phenom-enon.

All of these insights weremade possible by researchled by Fred “Rusty” Gage ofthe Salk Institute for Bio-logical Studies in La Jollaand Peter Eriksson of Sahl-grenska University Hospi-tal inGothenburg, Sweden.

In 1998, they made thegroundbreaking discoverythat the human hippocam-pus, a part of the brain in-volved inmemory, producesnew neurons throughoutlife.

Further research not on-ly confirmed that conclu-sion, it established that newbrain cells are generated inother parts of the brain.

Moreover, studies havefound that highly educatedpeople generally have a low-er risk of Alzheimer’s dis-ease. While correlationdoesn’t automaticallymeancausation, theseconverginglines of evidence increasing-ly suggest that vigorousmental and physical activ-ity protects against mentaldegeneration.

Earlier treatmentsIf neural regeneration

can be stimulated by in-creased intellectualactivity,some biochemical changesmust take place to producethis effect. So presumably,medications could be devel-oped to directly stimulatebrain growth and repair.

Tuszynski is an advocate

of that approach, usingwhat are callednervous sys-tem growth factors. Theseare chemicals promotingcell survival and functionthat become deficient be-cause of Alzheimer’s dis-ease, he said.

“One of the things we’retrying to do is not only re-place deficient growth fac-tors, but also provide extraamounts ... to try and pre-vent cell death and stimu-late cell function. And inanimal (testing), they’requite effective, and the ef-fects are replicated acrossmany different academiclaboratories.”

In the longer term, scien-tists want to understandjust what causes Alzheim-er’s. While the disease isage-related, it’s far from aninevitable part of aging.People can remain lucidwell into their 90s and be-yond, although some dete-

rioration of memory andthinking generally occurs.

During the past two dec-ades, scientists have con-centrated on two majormechanisms linkedwith theonset of Alzheimer’s. Bothof them deal with abnormalforms of proteins that playvital roles in how the brain’sneurons function.

One is a tangled form ofprotein called beta amyloid,which appears to accumu-late in neurons and damagethem. Several amyloid-re-moving drugs have beentested in people, with onlyverymodest signs that theycan slowdownAlzheimer’s.

One of the medications,solanezumab, is being test-ed in people 65 or older whodon’t have any Alzheimer’ssymptoms — to see if it canprevent the disease frommanifesting. More informa-tion is available at j.mp/so-ladcs.

A photo of a neu-ron is projectedon Alzheimer'sresearcher HuaxiXu at the San-ford BurnhamPrebys MedicalDiscovery In-stitute.

HOWARD LIPIN U-T

EDUARDO CONTRERAS U-T

RESEARCH • Scientists want to understand what causes disease

“If you learnsomething new,you build upmore synapsesin the brain.”Dr. Mark Tuszynski,director of UC San Diego’sCenter for Neural Repair

FROM SD1

By the numbers

5.3millionThe estimated number of Americans who had Alzheimer’s disease last year, including nearly590,000 in California and more than 60,000 in San Diego County. Experts said up to half of thesepatients haven’t been diagnosed with the affliction.

The number of new cases of Alzheimer’s and other dementias isprojected to double by 2050. In California, the doubling is expectedto occur by 2030.

60to80The percentage of all dementia cases nationwide attributed to Alzheimer’s disease.

Almost two-thirds ofAlzheimer’s patients intheU.S. arewomen.

$226billionLast year’s estimated bill for Alzheimer’s and other dementias. The figure included medical treatment,the expense of other support services and the lost financial productivity for family members and otherswho provide caregiving. By 2050, the annual cost is projected to reach $1.1 trillion.

Source: U-T research

The disease is the third-leading cause of deathin SanDiego Countyand the sixth nationally.

SD2 THE SAN DIEGO UNION-TRIBUNE SUNDAY • JANUARY 17, 2016

SD3THE SAN DIEGO UNION-TRIBUNE SUNDAY • JANUARY 17, 2016

The theory is that Alz-heimer’s is the end stage of along disease process, onethat builds for many yearsbefore symptoms show upclearly.

More and more, scien-tists are exploring the con-cept that drugs and othertherapies should be givenearlier in life, before themental damage becomesoutwardly obvious.

The other protein, tau, isalso believed to harm neu-rons when it becomes defec-tive.

Abnormal tau seems toallow structures called mi-crotubules to unravel. Mi-crotubules help maintainthe cytoskeleton, which inturn enables cells to moveand keep their shape orchange it.

New medications aimedat combating aberrant tauare entering clinical trials.Also, theU.S.FoodandDrugAdministration is consider-ing whether to let research-ers test whether certainmedications previously ap-proved for other diseasescan block the destruction ofdefective tau.

At the earliest, it will like-ly take a few years to deter-mine whether these drugsworkwell.

Another approach is todownplay theories of causa-tionand look forcompoundsthat demonstrate effective-ness inprotectingthebrain’sfunctions.

One significant line of in-quiry involves curcumin,which is found in a compo-nent of curry called turmer-ic. Research has shown thatcurcumin produces an anti-inflammatory effect, andbrain inflammation is ama-jor part of the Alzheimer’sprofile.

Working with that evi-dence, scientist DaveSchubert and his colleaguesat theSalkInstitutehavede-veloped a drug candidatethatnotonlyappears topro-tect against Alzheimer’s in amouse model, but also ex-erts a broader anti-aging ef-fect.

Diagnosing the livingBeforeanydiseasecanbe

treated, it must be diag-nosed. And identifying Alz-heimer’s has long been diffi-cult, at least in living pa-tients.

The telltale toll of betaamyloid plaques and tau-re-lated tangles were first dis-covered in an autopsy per-formed in 1906 by Aloysius“Alois”Alzheimer, the physi-cian who gave his name tothedisease.

Recently, the FDA ap-proved a test to detect betaamyloid plaques in livingpeople, and a similar test fortau is coming, said HuaxiXu, a researcher at the San-ford BurnhamPrebysMedi-cal Discovery Institute in LaJolla.

The amyloid test uses aradioactive isotope thatbinds to beta amyloid, mak-ing it visible through a PETscan.

Other diagnostic testsarebeingdevelopedtogainafiner readon thebrain’s con-dition, Xu said. This in-cludes examination of thecerebrospinal fluid, whichbathes the brain and pro-vides various types of sup-port to its cells.

Overall, it’s now possibleto screen people for signa-ture evidence of Alzheimer’swell before they show symp-tomsof thedisease.

“I think that’s one of themajor breakthroughs,” Xusaid.

In September, he and hiscolleagues published astudy indicating a possiblemechanism for tau degener-ation, the overabundance ofa protein called appoptosin.Other tau-associated dis-eases include frontal tempo-ral dementia and progres-sive supranuclear palsy, orPSP.

Anassortmentof factors,including those still to beidentified, is probably re-sponsible for the formationof Alzheimer’s, Xu said. Heenvisions scientists comingup with more diagnostictests and treatments to ac-count for these other influ-ences.

A comprehensive bat-tery of tests and cocktailsof drugs could be more ef-fective than treating isolat-ed dimensions of the dis-ease.

New wave of drugsUC San Diego’s Larry

Goldstein is both an Alz-heimer’s researcheranddi-rector of the university’sstemcellprogram.Hemar-ries the two fieldsby study-ing the Alzheimer’s proc-ess in neurons grown fromartificial embryonic stemcells.

Cultured in the lab, thesecells provide a “disease in adish” model that allows sci-entists toexamine thedevel-opment of neuronswith var-ious risk factors forAlzheim-er’s disease. They also pro-vide a new way for testingpotential drugs.

With a particular kind ofstem cell technology, re-searcherscantakeskinsam-ples from Alzheimer’s pa-tients and turn them intobrain cells. This approachgives them unprecedentedinsights into the pathologyof the disease. (It’s a viola-tion of scientific ethics toopen up a living person’sbrain to extract cell sam-ples.)

Goldstein’s lab is study-ing the brain cells of J. CraigVenter of La Jolla, the genet-ics and genomics pioneer,that were obtained usingsuch stem cell technology.Venter learned years agothathehasagenetic risk fac-

tor for Alzheimer’s, yet at 69remains mentally unim-paired.

Analysis ofVenter’s braincells has revealed howone ofthe known risk factors oper-ates,Goldstein said. The labhas compared Venter’sbrain-cell sample with sam-ples obtained from patientsat the Shiley-Marcos Alz-heimer’s Disease ResearchCenter inLaJolla.

“What we’ve also done istake his genome, and makechanges in thatgenome,andstudy how they change thebehavior of the cells andalsoscreen for new drugs,” Gold-stein said.

Testing with such cells,fromadefined genetic back-ground,gets ridofa lotof the“noise” in data from peoplewith divergent genetic back-grounds, he said. This helpsresearchers trace the com-plicated molecular path-ways that gene variants reg-ulate.

Ultimately, Goldsteinsaid, “There ishopethatnewapproaches underway willresult in new therapeutic in-terventions, but there is stilla greatdeal abouthowbraincells fail in this disease thatwe don't understand andmust understand before wecan implement therapiesthat significantly alter thecourse of the disease. I re-mainhopeful but soberedbythe difficulty of the prob-lem.”

bradley.fikes@sduniontribune.com(619) 293-1850Twitter: @sandiegoscience

Source: U.S. Department of Health and Human Services; Image courtesy of the National Institute on Aging/National Institutes of Health

AARON STECKELBERG & AARON ATENCIO U-T

How Alzheimer’s disease damages the brain

Healthybrain

SevereAlzheimer’sdisease

Extreme shrinkage of cerebral cortexLayer of folds and bulges seen on outer partof the brain. Influences memory, awareness,perception, language and consciousness.

Severely enlarged ventriclesVentricles are spaces in the brain filled withcerebrospinal fluid, which helps cushion thebrain and provide nutrients.

Extreme shrinkage of hippocampusArea of the brain thought to be the center ofemotion, memory and the autonomic nervoussystem, which controls actions such asbreathing, heartbeats and digestion.

Extreme shrinkage of entorhinal cortexResearch has shown that Alzheimer’sdamage starts in this region of the brain.

Facts about Alzheimer’s

Alzheimer’s is a neurodegenerative illness that causesphysical and mental symptoms. Physically, neurons aregradually damaged and then die. The damage is associ-ated with tangled protein deposits called amyloid betaand another protein called tau, although other factors arelikely involved. When these proteins become defective,they harm neurons.

With this destruction, the brain begins to shrink. Thechanges are visible through imaging technology or withan autopsy.

Alzheimer’s disease starts decadesbefore symptoms emerge, according toa growing body of evidence. Thismeans prevention and treatment effortsmay have to start well before symp-toms arise in order to be effective.

Symptoms appear slowly. In the early stages, progres-sive loss of short-term memory begins to interfere withdaily life. Routine tasks, such as driving to a familiarlocation, become more difficult. As the disease progress-es, long-term memory fails. Patients struggle to finddesired words and carry on conversations. They forgetimportant events in their lives, and even people well-known to them become strangers. Their moods maychange and fluctuate; depression, social withdrawal,suspicion and hostility sometimes emerge.

Unintentional mistreatment often makes the conditionworse. Alzheimer’s care centers may have their residentsfollow a set daily regimen, such as adhering to specificwaking and sleeping hours, eating a certain range offoods and engaging in programmed activities. Thesecould take away the patients’ remaining sense of inde-pendence. Experts say sedation is needed in some cases,but only as a last resort.

The risk of Alzheimer’s goes up with age, but the rela-tionship is imperfect. The disease can strike in middleage or even earlier. Conversely, many people in their 80sor even 90s retain clear minds. Other forms of dementiaappear more often with age.

Genetics can influence the risk of Alzheimer’s. There isone extremely rare form of the disease that’s clearlylinked to genetics: People with this genetic variant arevirtually certain to develop Alzheimer’s. It’s unclear howpertinent this form is in studying the far more common“sporadic” Alzheimer’s, in which genes appear to play alesser role.

Of the 10 leading causes of death inthe United States, Alzheimer’s diseaseis the only one that has neither a curenor an effective treatment.

No medication or other therapy currently available canreverse or even stop the progression of Alzheimer’s.Some drugs provide temporary benefits, but the neuro-degeneration underlying the disease continues. Numer-ous attempts to develop Alzheimer’s drugs to fight amy-loid buildup have failed.

BRADLEY J. FIKES

Resources

Alzheimer’s Association,San Diego-Imperial chap-ter: alz.org/sandiego or(800) 272-3900

Alzheimer’s San Diego:alzsd.org or (858) 492-4400

U.S. Department ofHealth and Human Ser-vices: alzheimers.gov

National Institute onAging: overview fact sheetabout Alzheimer’s diseaseat 1.usa.gov/1IoRcXo or(800) 438-4380

Alzheimer’s Foundationof America: alzfdn.org or(866) 232-8484

Alzheimer’s Forum:alzforum.org

San Diego Elder CareCenter: sandiegoelderlaw-.com or (619) 235-4357

Elder Law & Advocacy:seniorlaw-sd.org or (858)565-1392

Southern CaregiverResource Center: caregi-vercenter.org or (858)268-4432

Alzheimer’s carecenters may havetheir residentsfollow a set dailyregimen, such asspecific wakingand sleepinghours, eatingcertain foods andengaging in regu-lar activities.

NELVIN C.CEPEDA U-T

“There is hopethat newapproachesunder waywill resultin newtherapeuticinterventions,but there isstill a greatdeal abouthow braincells fail inthis diseasethat we don'tunderstand”Larry Goldstein, Alzheimer’sresearcher and director of UCSan Diego’s stem cell program

EARNIE GRAFTON U-T